Next generation sequence-based targeted somatic mutation analysis in thyroid nodules with pathologically diagnosed as indeterminate cytology.

PURPOSE: The management of indeterminate thyroid nodules remains a topic of ongoing debate, particularly regarding the differentiation of malignancy. Somatic mutation analysis offers crucial insights into tumor characteristics. This study aimed to assist the clinical management of indeterminate nodules with somatic mutation analysis. METHODS: Aspiration samples from 20 indeterminate thyroid nodules were included in the study. A next-generation sequencing panel containing 67 genes was used for molecular profiling. The results were compared with pathology data from surgical material, which is considered the gold standard. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. RESULTS: Variants in six genes (NRAS, BRAF, TP53, TERT, PTEN, PIK3CA) were detected in 10 out of 20 samples. We identified nine Tier 1 or 2 variants in 10 (67 %) out of 15 malignant nodules (NRAS, BRAF, TP53, TERT, PTEN, PIK3CA) and one Tier 2 (PIK3CA) variant in one out of five benign nodules. The study demonstrated an NPV of 40 %, a PPV of 90 %, a specificity of 80 %, and a sensitivity of 60 %. CONCLUSION: Based on the detected molecular markers, at least nine patients (45 %) could be managed correctly without needing a repeat FNAB attempt. This study underscores the clinical practicality of molecular tests in managing nodules with indeterminate cytology. Additionally, this study emphasizes the importance of considering the patient's age when determining the DNA- or RNA-based genetic testing method. Finally, we discussed the significance of the somatic mutation profile and its impact on the current pathological classification.

Prognostic impact of mitosis and necrosis in non-mucinous lung adenocarcinomas and correlation with IASLC grading system.

BACKGROUND: In 2020, the International Lung Cancer Study Group (IASLC) Pathology Committee established a grading system for non-mucinous primary lung adenocarcinomas. This grading system is based on whether areas of high-grade patterns are present in more than 20% of the tumor. Parameters, such as necrosis, mitotic activity, lymphovascular invasion (LVI) and spread through air spaces (STAS), are excluded from evaluating the grading system. METHODS: A total of 217 patients' lung resection materials for primary lung adenocarcinoma were re-reviewed using the IASLC grading system. Necrosis, mitotic activity, LVI status and STAS were also evaluated in the resection materials, aiming to demonstrate the relationship between these histopathological features and clinical outcome data. RESULTS: At all stages, overall survival (OS) and recurrence-free survival (RFS) were related to grade (p=0.011 and 0.024, respectively). Additionally, patients with necrosis were associated with worse OS and RFS (p=0.002 and 0.048, respectively). When grade 2 and 3 tumors were analyzed individually, a significant relationship was found between necrosis and OS in grade 3 tumors (p=0.002). Patients with a high mitotic count (≥10/10 high-power fields) had significantly worse OS (p=0.046). The prevalence of LVI and STAS increased with grade; however, their prognostic significance has not been demonstrated. CONCLUSIONS: The new grading system provides a highly efficient prognostic classification for survival. Necrosis and high mitotic count are important prognostic parameters for survival. Additionally, necrosis is a stage-independent prognostic factor for OS in grade 3 tumors, although no effect on prognosis can be demonstrated in grade 2 tumors.

Immunotherapy-induced granulomatous reaction in patients with melanoma.

Immune checkpoint inhibitors (ICIs) represent a new era in stage IV melanoma treatment. These agents are generally well tolerated but have specific side effects. The granulomatous reaction is one of such ICI-related adverse events. In this report, we present the cases of three patients with stage IV melanoma who all developed mediastinal and hilar lymphadenopathy during ICI treatment. While a complete response was observed in one patient, near complete responses were observed in the other two patients. Amid these favorable outcomes, all patients developed mediastinal and hilar lymphadenopathy approximately 6 months after the initiation of immunotherapy. Biopsies were performed to explore the underlying pathology of the lymph nodes, which revealed granulomatous reactions rather than metastases. Hence, immunotherapy was continued in all patients. The development of granulomatous lymphadenitis associated with ICIs may mimic disease recurrence/progression clinically and radiographically. Awareness of such type of adverse event is crucial to decide whether to continue therapy or not.

Childhood trauma and general cognitive ability: Roles of minimization/denial and gender.

The aim of this study was to investigate the effects of minimization and gender on the interaction between childhood trauma and general cognitive ability. The study included 345 students. The data were obtained via an information form, the Childhood Trauma Questionnaire (CTQ), and Raven's standard progressive matrices (RSPM). The mean CTQ total score and the mean sexual abuse, physical, and emotional neglect subscale scores of the male students were significantly higher than those of the female students (p<0.05). The mean minimization score of the female students was greater than that of the male students (p<0.05). However, among the female students with minimization scores of 3, there was a moderate and significant negative correlation between the CTQ and RSPM scores (r=-0.533, p<0.05). This study found that general cognitive ability was influenced by childhood trauma among female students with higher minimization/neglect scores. The results of the current study suggest that ignoring the effects of minimization may be a misleading factor for determining the gender ratio of childhood trauma and evaluating its effect on long-term cognitive functions.

Factors associated with suicide attempts in patients with bipolar disorder type I.

BACKGROUND: The aim of this study is to identify the risk factors that are associated with suicide attempts in patients with bipolar disorder type I. SUBJECTS AND METHODS: This cross-sectional study was conducted with inpatients and outpatients with BD type I. Patients who met the study inclusion criteria (n=91) were evaluated in terms of sociodemographic variables, history of childhood trauma, comorbidity of adult attention deficit hyperactivity disorder and posttraumatic stress disorder, and the course of the disease. The patients were divided into two groups: those with a history of suicide attempts and those without a history of suicide attempts. The parameters of the study groups were compared with t and chi-square tests as appropriate. Logistic regression was used to identify the predictors of suicide attempt. RESULTS: Logistic regression analysis of the study parameters suggested that the number of major depressive episodes (odds ratio: 7.18; 95% confidence interval: 1.84-28) and history of emotional neglect (odds ratio: 1.83; 95% confidence interval: 1.15-2.90) were significant predictors of suicide attempt in patients with BD. CONCLUSION: In BD type I patients with a history of suicide attempts, the number of depressive episodes and emotional neglect, a subtype of childhood traumas, were the most remarkable risk factors. Considering the frequency of depressive episodes during the course of the disease and assessing traumas including those in childhood may help predict future suicide attempts in patients with BD.