Fine-needle biopsy of thyroid nodules and the contribution of molecular analysis of BRAF and RAS mutations.

BACKGROUND: Thyroid cancer is the most common endocrine malignancy. There is a significant overdiagnosis of thyroid carcinomas that would never clinically manifest, with consequent unnecessary surgical treatment. The fine-needle biopsy and subsequent cytologic examination is of crucial importance in the differential diagnosis of thyroid nodules. On the other hand, a significant portion of the results are indeterminate. OBJECTIVE: To assess the relationship of BRAF/RAS mutations in biopsy specimens to histological characteristics of thyroid nodules in individuals who undergone fine-needle biopsy and surgery. METHODS: This cross-sectional study involves 170 subjects with indeterminate cytology analyzed for BRAF/RAS mutations. RESULTS: Of all 170 patients with indeterminate cytological finding, 103 were indicated for surgery. Of these, 31 were BRAF and 25 RAS positive. Thyroid cancer was diagnosed in 59 patients, while 44 patients had non-malignant thyroid lesions. The BRAF V600E mutation was detected in 30 patients, and the RAS (K-RAS, N-RAS, and H-RAS) mutation in 13 patients with thyroid cancer. In all BRAF-positive nodules, thyroid cancer was histologically confirmed. This means a 100 % positive predictive value of BRAF testing in our study. CONCLUSION: Stratification of thyroid lesions with uncertain results of fine-needle cytology using genetic markers can help to deliver more tailored medical treatment (Tab. 6, Ref. 19).

Influence of autoimmune thyroiditis on the prognosis of papillary thyroid carcinoma.

OBJECTIVES: The association of autoimmune thyroiditis (AIT) with papillary thyroid carcinoma (PTC) has been studied for over 60 years, yet their causal relationship has not been elucidated. Most published papers report a better prognosis of the patients with tumour in the field of thyroiditis. In our work we aimed to find out the differences in the clinical behaviour of PTC depending on the presence of autoimmune inflammation. METHODS: We retrospectively analysed a group of 1,201 patients with PTC dispensed in St. Elisabeth Cancer Institute and Faculty of Medicine from 2000 to 2015. We divided patients with AIT according to the time of diagnosis of inflammation into the AIT1 subgroup, which included patients monitored for AIT before tumour detection. In them, we assumed that the factor of long-term endocrinological monitoring could speed up the diagnosis of the tumour and thus improve the prognosis. The AIT2 subgroup consisted of patients with both tumour and inflammation diagnosed simultaneously, thus eliminating the factor of prior monitoring. RESULTS: PTC in the AIT1 subgroup had better prognostic parameters (TNM stage, persistence, disease remission). Patients in the AIT2 group had all monitored parameters comparable with patients with tumours without autoimmune inflammation. CONCLUSION: AIT alone does not have a protective effect on the course of PTC, the cause of a better prognosis in the AIT1 subgroup is a different pathomechanism of carcinogenesis, as well as previous endocrinological monitoring and earlier detection of malignancy (Tab. 4, Fig. 2, Ref. 27).

Diagnostic ipsilateral central neck dissection may reduce undertreatment of initially low-risk papillary thyroid cancer.

Although small papillary thyroid cancer (PTC) patients are considered as low-risk population, approximately 5-20% of these patients relapse after surgery. The objective of this single-center retrospective study was to identify risk factors, which could help to distinguish patients who would need additional treatment after surgery. A total of 268 patients (39 men, 229 women, median age 49 years) underwent surgery between 2007-2015, and fulfilled inclusion criteria: tumor size ≤20 mm, absence of metastatic lymph nodes (LN) in the lateral neck compartment (LC), and absence of local invasion. Total thyroidectomy was performed in 252 cases, in 221 cases with central neck compartment (CC) dissection. The outcome - a more aggressive disease - was defined as the presence of metastases in the LNLC or in distant organs found during follow-up. A median follow-up was 117 months. Overall, 41 patients experienced the outcome with a median time-to-event of 18 months. Male gender (OR=2.2, p=0.049), extra-thyroidal extension ETE (OR=2.61, p=0.015), and metastases in LNCC (OR=4.21, p<0.001) were associated with worse outcome. Multivariable analysis and stratification according to ETE revealed an effect modification with a higher effect of the positive LNCC on the outcome among patients without ETE than in those with ETE. Our findings advocate placing greater emphasis on the role of LNCC metastases in the absence of ETE. In clinically node-negative tumors intraoperative examination of CC on the side of the tumor followed by CC dissection if metastatic lymphadenopathy is present could play an important role in the stratification of patients with small-size PTC.

An incidental finding of pheochromocytoma in a 33-year-old patient with Lynch syndrome.

Pheochromocytoma is a catecholamine-producing neuroendocrine tumor arising from chromaffin cells of the adrenal medulla. The detection of these tumors is extremely important because they are associated with high cardiovascular morbidity and mortality. Progress in molecular genetics has revealed that up to 35% of pheochromocytomas are inhereted. Lynch syndrome (hereditary nonpolypous colorectal cancer - HNPCC) is an autosomal dominant genetic condition that is associated with a high risk of colorectal cancer or other extracolonic tumors (adenocarcinoma of endometrium, stomach, ovarian carcinoma, carcinoma of urinary tract, small intestine, brain tumors and skin cancer). Foreign medical journals are reporting an increasing number of cases on coexistence of HNPCC and neuroendocrine tumors, including pheochromocytoma. It increases the likelihood that this type of tumor could represent an additional extracolonic manifestation of Lynch syndrome.

Causal associations of autoimmune thyroiditis and papillary thyroid carcinoma: mRNA expression of selected nuclear receptors and other molecular targets.

Potential causal associations of autoimmune thyroiditis (AIT) and papillary thyroid carcinoma (PTC) have been studied previously. The mRNA expression patterns of thyroid hormone receptors (TR), retinoid receptors (RAR), rexinoid receptors (RXR), dihydroxyvitamin D3 receptors (VDR), and progesterone receptors (PR) in PTC tissue of patients without autoimmune thyroiditis (PTC/AIT-) and in PTC tissue of patients with coexisting AIT (PTC/AIT+) have been investigated in order to judge whether the observed changes may take part in the promotion and progression of thyroid cancer. Tumours with or without AIT were classified histologically and the semiquantitative PCR was performed. The results revealed that there was decreased expression of TRα, TRßα, RARα and PR mRNA in PTC/AIT+ tumours when compared with PTC/AIT- tumours. Decreased expression of RARα in PTC/AIT+ was detected when compared with PTC/AIT- patients. A similar effect of AIT was observed with a decrease in RARγ expression in PTC/AIT+ patients. On the other hand, there was an increased expression of VDR in thyroid tumours (PTC/AIT+) when compared with PTC/AIT-. PR mRNA was decreased in the thyroid tumours of PTC/AIT+ patients when compared with PTC/AIT- patients. In addition, there was an increased expression of MKi67 and complement C3 in PTC of PTC/AIT+ when compared with PTC/AIT-. In the PTC/AIT+ group, a decreased level of IGF-1 mRNA was found when compared with the PTC/AIT- group. According to the significant differences of the studied markers in PTC/AIT+ compared with PTC/AIT-, it was indicated that AIT may be a predisposing factor for the development of PTC.

[The course of differentiated thyroid microcarcinoma in patients treated by different therapeutic strategies]. / Priebeh ochorenia u pacientov s diferencovaným mikrokarcinómom stítnej zlazy pri pouzití rôznych liecebných postupov.

Low risk differentiated thyroid microcarcinoma therapy is a controversial area of thyroid tumor management. Major international medical societies and reputable institutes consider lobectomy to be sufficient therapeutic intervention for the pT1a cN0cM0 stage of papillary thyroid microcarcinoma. However different views and therapeutic strategies exist and result in unnecessary overtreatment and worsening of patients quality of life. We researched the course of the differentiated thyroid microcarcinoma in patients using different therapeutic strategies: lobectomy, total thyroidectomy, total thyroidectomy with central compartment prophylactic lymphadenectomy and total thyroidectomy followed by radioactive iodine treatment. Apart from an excellent prognosis we did not find out any clinically significant differences in the course of the disease. We can conclude that lobectomy is sufficient therapeutic intervention for patients with differentiated thyroid microcarcinoma without known metastases.Key words: differentiated thyroid microcarcinoma - management - overtreatment - the course of the disease.

Secondary hypothyroidism in hereditary hemochromatosis: recovery after iron depletion.

We report the case of a 56 year old male with hereditary haemochromatosis complicated by hepatic cirrhosis, insulin treated diabetes mellitus, hypogonadism and secondary hypothyroidism, the latter which was corrected by iron depletion. This is only the second such case to be reported.