A Significance of Concomitant BRAFV600E and TERT Mutations in Polish Patients with Papillary Thyroid Microcarcinoma: A Retrospective Cohort Study Based on 430 Cases.

Background: The incidence of papillary thyroid cancer is increasing worldwide due to more frequent pathological detection of papillary thyroid microcarcinomas (PTMC), which are cancers measuring 1 cm or less in diameter. In rare cases, the course of PTMC can be aggressive, with an increased risk of recurrence/persistent disease. The aim of this study of Polish patients diagnosed with PTMC was to assess the impact of concomitant B-type Raf kinas-activating mutation in codon 600 of exon 15 (BRAFV600E) and telomerase reverse transcriptase (TERT) hotspot mutations on clinicopathological features, response to treatment, potential recurrence, and the final outcome. Methods: A retrospective analysis of the 430 PTMC cases diagnosed during 2001-2020 at a single center was performed. All PTMC cases were assessed histopathologically, and analyses of BRAFV600E and TERT promoter were performed based on DNA isolated from tumor blocks. Results: There were 29/430 (6.7% [confidence interval: 4.6-9.5]) patients in whom the TERTC228T and/or TERTC250T mutations coexisted with the BRAFV600E mutation. A statistical comparison between PTMC cases with concomitant BRAFV600E and TERT hotspot mutations and those without any of those mutations revealed no significant differences between the two groups with respect to risk stratification, response to primary treatment, clinical course, or final disease status. Conclusion: Regardless of the molecular background of PTMC, the overall response to therapy is excellent, and long-term disease-free survival rates can be achieved by most patients.

Is Male Sex A Prognostic Factor in Papillary Thyroid Cancer?

Identifying risk factors is crucial for predicting papillary thyroid cancer (PTC) with severe course, which causes a clinical problem. The purpose of this study was to assess whether male sex can be such a predictive factor and to verify whether including it as a predictive factor of high initial risk of recurrence/persistence would help to enhance the value of the American Thyroid Association initial risk stratification system (ATA). We retrospectively analyzed 1547 PTC patients (1358 females and 189 males), treated from 1986 to 2018. The relationship between sex and clinicopathological features, response to therapy, and disease status was assessed. Men with PTC showed some adverse clinicopathological features more often than women, including angioinvasion, lymph node metastases, and tumor size > 40 mm. There were sex-related disparities with respect to response to initial therapy and final follow-up. Male sex is associated with some unfavorable clinicopathological features of PTC, which may affect response to initial therapy or final disease status. In our study, modification of the ATA system by including male sex as a risk factor does not enhance its value. Thus, further studies are needed to assess whether males require treatment modalities or oncological follow-up protocols that are different from those of females.

Incidence of the CHEK2 Germline Mutation and Its Impact on Clinicopathological Features, Treatment Responses, and Disease Course in Patients with Papillary Thyroid Carcinoma.

The CHEK2 gene is involved in the repair of damaged DNA. CHEK2 germline mutations impair this repair mechanism, causing genomic instability and increasing the risk of various cancers, including papillary thyroid carcinoma (PTC). Here, we asked whether CHEK2 germline mutations predict a worse clinical course for PTC. The study included 1547 unselected PTC patients (1358 women and 189 men) treated at a single center. The relationship between mutation status and clinicopathological characteristics, treatment responses, and disease outcome was assessed. CHEK2 mutations were found in 240 (15.5%) of patients. A CHEK2 I157T missense mutation was found in 12.3%, and CHEK2 truncating mutations (IVS2 + 1G > A, del5395, 1100delC) were found in 2.8%. The truncating mutations were more common in women (p = 0.038), and were associated with vascular invasion (OR, 6.91; p < 0.0001) and intermediate or high initial risk (OR, 1.92; p = 0.0481) in multivariate analysis. No significant differences in these parameters were observed in patients with the I157T missense mutation. In conclusion, the CHEK2 truncating mutations were associated with vascular invasion and with intermediate and high initial risk of recurrence/persistence. Neither the truncating nor the missense mutations were associated with worse primary treatment response and outcome of the disease.

Did Introducing a New Category of Thyroid Tumors (Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features) Decrease the Risk of Malignancy for the Diagnostic Categories in the Bethesda System for Reporting Thyroid Cytopathology?

In 2016, Nikiforov et al. (JAMA Oncol 2:1023-1029, 2016) proposed replacing the term "non-invasive encapsulated follicular variant of papillary thyroid carcinoma" (FVPTC) with the term "non-invasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP). In 2018, to avoid the misdiagnosis of papillary thyroid cancer as NIFTP, the authors proposed changes to the criteria for NIFTP classification. Some previous studies evaluated the impact of NIFTP on the risk of malignancy (ROM) in the fine-needle aspiration cytology (FNAC) diagnostic categories according to the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). However, little is known about the influence of an NIFTP diagnosis on ROM on the basis of the revised criteria. The aim of this study was to assess the influence of NIFTP on ROM using the revised diagnostic criteria. The present study included 998 thyroid nodules that were diagnosed and resected at the same medical center. All specimens with a diagnosis of cancer were reviewed to identify NIFTP according to the revised 2018 criteria. Additionally, molecular diagnostics were performed to detect the BRAF p.V600E mutation and TERT promoter mutations in all the NIFTP cases. The number of cases that met the revised criteria was determined, and the ROM was calculated in each of the FNAC diagnostic categories. Only five cases (2.3% of all papillary thyroid carcinoma diagnoses) were considered NIFTP, according to the 2018 criteria. With respect to the FNAC category, one case was a follicular neoplasm or suspicious for a follicular neoplasm (FN/SFN), three cases were suspicious for malignancy (SM), and one case was malignant (M). The ROM decreased in each of the Bethesda categories (0.7% in FN/SFN, 4.3% in SM, and 0.5% in M) when a diagnosis of NIFTP was taken into account. These reductions were not statistically significant. These data indicate that the NIFTP entity has very little impact on ROM for the diagnostic categories of the Bethesda system.

Does the TT Variant of the rs966423 Polymorphism in DIRC3 Affect the Stage and Clinical Course of Papillary Thyroid Cancer?

Thyroid cancer (TC) is the most common cancer of the endocrine system. Most new diagnoses are of low-grade papillary thyroid cancer (PTC), suggesting that PTC may be over-diagnosed. However, the incidence of advanced-stage PTC has increased in recent years. It is therefore very important to identify prognostic factors for advanced PTC. Somatic mutation of the BRAF gene at V600E, or the coexistence of the BRAF V600E mutation and mutations in the TERT promoter are associated with more aggressive disease. It would also be valuable to identify genetic risk factors affecting PTC prognosis. We therefore evaluated the impact of the rs966423 polymorphism in the DIRC3 gene, including its relationship with unfavorable histopathological and clinical features and mortality, in differentiated thyroid cancer (DTC). The study included 1466 patients diagnosed with DTC from one center. There was no significant association between the DIRC3 genotype at rs966423 (CC, CT, or TT) and any histopathological or clinic factor examined, including initial response to therapy, response at follow-up, or overall mortality, in DTC patients.

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.

[Quality of life in patients with orbitopathy - single center experience]. / Jakosc zycia chorych z orbitopatia tarczycowa.

Thyroid-associated orbitopathy is a syndrome of eye symptoms produced by immunological inflammation of soft tissues of orbit,mostly due to Graves-Basedow disease. This disease is accompanied by proptosis, oedema of lids, double vision, tearing and photophobia. These symptoms lead to significant deterioration of quality of life due to reduction of sharpness of sight and therefore worsen emotional condition of patients. AIM: The aim of study was to assess the impact of Graves orbitopathy on quality of life. Additional aim was assessement of deppression among the subjects. MATERIALS AND METHODS: Study in form of anonymous modified questionnaire EUGOGO grading quality of life of patients with thyroidassociated orbitopathy and the scale of depression by Beck - carried out directly among 30 patients of Clinic od Endocrinology of the Medical Univeristy of Lódz (22 female and 8 male) from November 2011 to April 2012. RESULTS: Patients with thyroid-associated orbitopathy have considerably reduced quality of life - carried out qestionnaires showed they have problems with everyday activity like: riding bicycle (17 patients - 57%), driving car (14 patients - 45%), moving in apartment and outside (9 patients - 30%), watching TV (21 patients - 17%) and reading books (25 patients - 83%). Furthermore, many patients with thyroidassociated orbitopathy have serious emotional disorders - 20 persons have symptoms of depression. CONCLUSIONS: Graves orbitopathy have negative influence on quality of life. Orbitopathy worsens self-evaluation of patients, their interpersonal contacts, making new acquaintances, working and finding new job. Furthermore, many patients with thyroid-associated orbitopathy have serious emotional disorders. It seems reasonable to include psychotherapist in the therapeutic process.