The influence of the reclassification of NIFTP as an uncertain tumour on risk of malignancy for the diagnostic categories according to the Bethesda system for reporting thyroid cytopathology

Introduction: The noninvasive encapsulated, follicular variant of papillary thyroid carcinoma was reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). The exclusion of NIFTP from the group of malignant tumours decreases the risk of malignancy (RoM) as defined by the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). The aim of the present study was to evaluate the RoM for each category in TBSRTC with and without exclusion of NIFTP from the tally of malignancies. Material and methods: The present study included 998 thyroid nodules cases. All patients underwent diagnostic tests, including fine-needle aspiration cytology, and received surgical treatment. Slides for all resection specimens with a diagnosis of cancer were reviewed to identify NIFTP. The RoM for each of the categories in TBSRTC with and without exclusion of NIFTP from the malignant tumours was evaluated. Results: The RoM decreased with the exclusion of NIFTP from malignant categorisation with the following values for the different TBSRTC categories: non-diagnostic (ND): 0%; benign: 0%; atypia/follicular lesion of undetermined significance (AUS/FLUS): 1.6%; follicular neoplasm/suspicious for follicular neoplasm (FN/SFN): 0.7%; suspicious for malignancy (SUS): 6.9%; and malignant: 2.5%. The difference of 2.5% in the malignant category was statistically significant (p = 0.0253). Conclusions: The RoM for specific TBSRTC categories needs to be defined for each treatment centre because it is important for the selection of the appropriate surgical treatment for thyroid tumours

Przydatność określania obecności mutacji BRAF V600E w biopsji aspiracyjnej celowanej cienkoigłowej w zmianach niezdeterminowanych

  Introduction: Fine-needle aspiration biopsy (FNAB) is regarded as the gold standard method for the diagnosis of thyroid nodules, but it has its limitations. Additional methods that would improve sensitivity and specificity in the diagnosis of thyroid cancer (TC), especially in indeterminate lesions. Molecular tests seem to be such a tool. BRAF V600E mutation (the most common in TC) can be detected in FNAB and can be potentially a very useful ancillary marker for FNAB practice. The aim of our study was to evaluate the usefulness of the detection of the BRAF V600E mutation in FNAC in the early diagnosis of TC in patients with indeterminate cytology. Material and method: 2290 FNAB were performed and 147 indeterminate results (group 3, 4, and 5 of the Bethesda system) were obtained. Material from these groups was submitted for molecular tests for the occurrence of BRAF V600E mutation. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the tests were calculated. Results: Determining the presence of BRAF V600E mutation in FNAC material in groups 3 and 4 together and in group 5 is associated with sensitivity of TC diagnosis of 37.5% and 81.8%, respectively. In all cases the detection of BRAF V600E mutation was associated with histopathologically proving the presence of TC (specificity of the test — 100%). Conclusions: The presence of BRAF V600E mutation in FNAC material is always associated with the presence of TC. The usefulness of determining the presence of BRAF V600E in FNAC in cytological groups 3 and 4 is associated with low sensitivity in the diagnosis of thyroid cancer. Due to its high specificity BRAF V600E study may be useful in determining the scope of surgery in patients in cytological group 5. (Endokrynol Pol 2016; 67 (1): 41–47)    Wstęp: Biopsja aspiracyjna celowana cienkoigłowa (BACC) jest uznawana za złoty standard w diagnostyce guzków tarczycy. Ma ona jednak swoje ograniczenia. Poszukiwane są więc dodatkowe metody, które poprawiłyby czułość i specyficzność diagnozowania raka tarczycy, zwłaszcza w przypadku zmian niezdeterminowanych w BACC. Badania molekularne wydają się być takim narzędziem. Mutacja BRAF V600E (najczęstsza w raku tarczycy) może być wykrywana w materiale z biopsji i może wspomagać BACC w rozpoznawaniu raka tarczycy. Celem pracy była ocena przydatności wykrywania mutacji BRAF V600E w BACC w zmianach niezdeterminowanych we wczesnej diagnostyce pacjentów ze zmianami ogniskowymi w tarczycy. Materiał i metody: Przeprowadzono 2290 BACC, uzyskując w 147 próbkach wyniki niezdeterminowane (grupy 3, 4 i 5 wg klasyfikacji Bethesda). W grupie tej przeprowadzono badania molekularne w kierunku występowania mutacji BRAF V600E. Obliczono czułość, swoistość, wartość predykcyjną dodatnią, wartość predykcyjną ujemną i dokładność testu. Wyniki: Obecność mutacji BRAF V600E w grupach cytologicznych 3 i 4 łącznie oraz w grupie 5 wiązała się z czułością w rozpoznawaniu raka tarczycy odpowiednio 37,5% i 81,8%. W każdym przypadku wykrycia mutacji BRAF V600E w badaniu pooperacyjnym rozpoznano raka tarczycy (specyficzność testu —100%). Wnioski: Obecność mutacji BRAF V600E w materiale BACC jest zawsze związana z obecnością RT. Przydatność określenia obecności BRAF V600E w BACC w grupach cytologicznych 3 i 4 jest związana z niską czułością rozpoznania RT. Ze względu na wysoką specyficzność BRAF V600E badania mogą być przydatne w określaniu zakresu operacji u pacjentów z grupy cytologicznej 5. (Endokrynol Pol 2016; 67 (1): 41–47)

Relationship between the Expression of CHK2 and p53 in Tumor Tissue and the Course of Papillary Thyroid Cancer in Patients with <i>CHEK2</i> Germline Mutations

The aim of this study was to determine whether the expression of CHK2 and p53 in tumor tissue in carriers of germline CHEK2 mutations can serve as a prognostic marker for PTC, and whether CHEK2 and TP53 copy numbers correlates with the course of PTC disease. This study included 156 PTC patients previously tested for the presence of CHEK2. Clinicopathological features, treatment response, disease outcome, and germline mutation status of the CHEK2 gene were assessed with respect to CHK2 and p53 expression, and CHEK2 and TP53 gene copy statuses. In patients with and without a germline mutation in CHEK2 and with higher CHK2 expression, the chances of an excellent treatment response and no evidence of disease were lower than in patients without or with lower CHK2 expression. TP53 deletion was associated with angioinvasion. In patients with a truncating mutation, the chance of a CHEK2 deletion was higher than in patients with WT CHEK2 alone or those with WT CHEK2 and with the missense I157T mutation. Higher CHK2 expression was associated with poorer treatment responses and disease outcomes. Higher CHK2 expression and positive p53 together with a TP53 deletion could be a prognostic marker of unfavorable disease outcomes in patients with germline truncating mutations in CHEK2