Thyroid fine-needle aspiration cytology: malignancy rate in the category of indeterminate significant atypia/indeterminate significant follicular lesion.

BACKGROUND: Fine needle aspiration cytology (FNAC) is a standard preoperative diagnostic modality for thyroid nodules. The Bethesda Thyroid Cytopathology Reporting System (TBSRTC) defines the FNAC atypia group as atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS). OBJECTIVES: Determine the risk of malignancy after surgical resection in patients with AUS/FLUS. DESIGN: Retrospective. SETTING: Pathology department of a tertiary care center. PATIENTS AND METHODS: All thyroid FNACs between 2015 and 2023 that were diagnosed as AUS/FLUS in Turkey. Patient demographics, preoperative ultrasonographic features, and follow-up data were collected. MAIN OUTCOME MEASURES: Relationship between AUS/FLUS diagnosis and final histopathological diagnosis. SAMPLE SIZE: 562. RESULTS: In total, 562 thyroid nodules were diagnosed as AUS/FLUS, and 267 (47.5%) were surgically excised. A malignant histopathological diagnosis was given in 28 cases (10.4%). Malignancy risk sensitivity of AUS/FLUS diagnosis was 75.68% (95% CI=58.80-88.23%), specificity was 55.24% (95% CI=50.91-59.52%), positive predictive value was 10.49% (95% CI=8.71-12.58%), and negative predictive value was 97.04% (95% CI=94.86-98.31%). In the ultrasonographic data, having symptomatic nodules, nodule calcification, and irregular nodule borders were all statistically significant signs of cancer in a one-variable analysis (P<.01). The presence of a family history emerged as a statistically significant prognostic marker for malignancy (P=.012). Although not statistically significant, the malignancy rate for nodules with nuclear atypia was 11.9%, significantly higher than the rate of 8.3% for nodules with architectural atypia only (P=0.32). CONCLUSIONS: The diagnosis of AUS/FLUS has a high rate of predicting the risk of malignancy and should continue to be offered. In addition to cytopathological features, ultrasound data and family history should be taken into consideration when evaluating the case. LIMITATIONS: Retrospective design and no molecular studies.

4-phenyl butyric acid improves hepatic ischemia/reperfusion and affects gene expression of ABC transporter Abcc5 in rats.

AIM: To assess the effects of 4-phenyl butyric acid (PBA) on oxidative stress, inflammation, liver histology, endoplasmic (ER) reticulum stress, and the expression levels of ATP-binding cassette transporter family members in a hepatic ischemia-reperfusion (IR) model. METHODS: Thirty-five rats were randomly divided into five groups: sham, IR, IR + 100 mg kg-1 PBA, IR + 200 mg kg-1 PBA, and IR + placebo. After sacrifice, we assessed serum biochemical variables, myeloperoxidase (MPO), malondialdehyde (MDA), total antioxidant status (TAS), and total oxidant status (TOS). The expression levels of Abcc (2 and 5), Abcg2, Abcf2, Ire1-α, and Perk genes were measured with a quantitative real-time polymerase chain reaction. RESULTS: Serum biochemical variables, MPO, MDA, TAS, and TOS levels of the PBA groups (especially in the low dose group) were lower than in the IR and placebo group (P<0.05). Histological tissue damage in the IR group was more severe than in the PBA groups. Ire1-α and Perk expression levels were significantly lower in the PBA groups than the IR group (P<0.001). Abcc (2 and 5) and Abcg2 expression levels were significantly lower in the IR group than in the sham and PBA groups (P<0.001, P<0.035, and P<0.009, respectively). CONCLUSIONS: The use of PBA significantly positively affected IR injury, which makes PBA a candidate treatment to reduce liver IR.

Association between Serum Carcino-embryonic Antigen Levels and Micropapillary Bladder Cancer Metastasis in an Elderly Male.

We, herein, present a case of a micropapillary variant of bladder cancer metastasizing to lymph nodes in an 87-year male with elevated serum carcinoembryonic antigen (CEA) levels (2637.8 ng/mL). The patient was evaluated for dyspeptic symptoms and elevated CEA levels. Colonoscopy and upper gastrointestinal endoscopy were normal. Contrast-enhanced computed tomography revealed a bladder tumour. Transurethral resection of bladder tumour (TUR-BT) was performed, and histologically, the tumour was reported as urothelial carcinoma (UC), high grade, and pT1. Intravesical Bacillus Calmette-Guérin (BCG) was started three weeks after TUR-BT and continued for two years. F-18 FDG PET/CT scans were performed every six months during the follow-up due to persistently elevated CEA levels. During follow-up, there was no recurrence of UC in the bladder. Two years later, he was admitted again with lymph node swelling in the left inguinal area. A tru-cut biopsy was performed, which showed UC with a micropapillary component. Gemcitabine monotherapy was given, which resulted in partial response, and a significant decline in serum CEA levels (490.17 ng/mL). Key Words: Carcinoembryonic antigen, Urothelial carcinoma, Bladder cancer, Micropapillary variant, Gemcitabine monotherapy.

DICER1 Mutations Occur in More Than One-Third of Follicular-Patterned Pediatric Papillary Thyroid Carcinomas and Correlate with a Low-Risk Disease and Female Gender Predilection.

Some pediatric papillary thyroid carcinoma (PPTC) cohorts have suggested a preliminary correlation with respect to DICER1 mutation status and histomorphology in both benign and malignant follicular cell-derived nodules; however, the data regarding correlates of DICER1-related sporadic PPTCs subtyped based on the 2022 WHO classification criteria are largely unavailable. The current study investigated the status of hotspot DICER1 mutations with clinical, histological and outcome features in a series of 56 patients with PPTCs with no clinical or family history of DICER1-related syndromic manifestation. Fifteen (27%) PPTCs harbored BRAF p.V600E. Eight (14%) cases of PPTCs harbored DICER1 mutations with no associated BRAF p.V600E. DICER1 mutations were identified in exons 26 and 27. A novel D1810del (c.5428_5430delGAT) mutation was also detected. We also confirmed the absence of hotspot DICER1 mutations in the matched non-tumor tissue DNA in all 8 DICER1-related PPTCs. The mean age of DICER1-harboring PPTCs was 15.1 (range: 9-18) years whereas the rest of this cohort had a mean age of 14.8 (range 6-18) years. With the exception of one PPTC, all DICER1-related PPTCs were seen in females (female-to-male ratio: 7). The female to male ratio was 3.8 in 48 DICER1-wild type PPTCs. In terms of histological correlates, 5 of 8 (63%) DICER1-mutant PPTCs were invasive encapsulated follicular variant papillary thyroid carcinomas (FVPTCs) including 4 minimally invasive FVPTCs and 1 encapsulated angioinvasive FVPTC, whereas the remaining 3 PPTCs were infiltrative classic papillary thyroid carcinomas (p < 0.05). The incidence of DICER1 mutations was 19.5% in BRAF p.V600E-wild type PPTCs. Sixty-three percent of DICER1 hotspot mutations occurred in invasive encapsulated FVPTCs, and this figure represents 38% of invasive encapsulated FVPTCs. Only one (12%) patient with DICER1-related disease showed a single lymph node with micro-metastasis. Unlike DICER1-wild type patients, no distant metastasis is identified in patients with DICER1-related PPTCs. The current series expands on the surgical epidemiology of somatic DICER1-related PPTCs by correlating the mutation status with the clinicopathological variables. Our findings underscore that female gender predilection and enrichment in low-risk follicular-patterned PTCs are characteristics of DICER1-related PPTCs.

The Place and Prognostic Value of TERT Promoter Mutation in Molecular Classification in Grade II-III Glial Tumors and Primary Glioblastomas.

OBJECTIVE: Diffuse gliomas, the most common primary malignant brain tumors, have been classified by the World Health Organization as class II-IV gliomas. After 2016, two mutations in the promoter region of the telomerase reverse transcriptase (TERT) gene were identified in addition to the IDH, 1p / 19q, and ATRX status. MATERIAL AND METHOD: We identified 84 patients with grade II-IV glioma with IDH, ATRX, 1p / 19q and TERT status. All tumor samples were subjected to molecular genetic screening (Sanger sequencing for IDH and TERT mutations, fluorescence in situ hybridization for 1p/19q status) after histological diagnosis (immunohistochemistry for IDH1 R132H, ATRX, and p53) for a more precise molecular diagnosis. The confidence intervals were calculated at the 95% confidence level, and differences at p < 0.05 were considered statistically significant. RESULTS: Primary glioblastomas had the highest frequency of TERT promoter mutations (25 of 28, 89.2%, p=0.006) followed by oligodendrogliomas (29 of 35, 82.8%, p < 0.001) while astrocytomas showed the lowest frequency (3 of 15, 20%, p=0.107), and the positivity significantly differed among these three groups (p < 0.001). TERT promoter mutations were more frequent in patients older than 55 years of age at diagnosis (p=0.023). The group with TERT promoter mutations, and without IDH mutations showed the worst overall survival. However, the presence of both TERT promoter and IDH mutations, which resembled oligodendroglial progression, showed best overall survival (p=0.042). CONCLUSION: The discovery of TERT promoter mutations in numerous gliomas has opened the door for a better molecular classification of gliomas, and TERT status is associated with survival. Further studies will help in elucidating the value of TERT promoter mutations as biomarkers in clinical practice, and eventual therapeutic targets.