Microcomputed tomography as a diagnostic tool for detection of lymph node metastasis in non-small cell lung cancer: A decision-support approach for pathological examination "A pilot study for method validation".

Background: Non-small cell lung cancer (NSCLC) patients without lymph node (LN) metastases (pN0) may exhibit different survival rates, even when their T stage is similar. This divergence could be attributed to the current pathology practice, wherein LNs are examined solely in two-dimensional (2D). Unfortunately, adhering to the protocols of 2D pathological examination does not ensure the exhaustive sampling of all excised LNs, thereby leaving room for undetected metastatic foci in the unexplored depths of tissues. The employment of micro-computed tomography (micro-CT) facilitates a three-dimensional (3D) evaluation of all LNs without compromising sample integrity. In our study, we utilized quantitative micro-CT parameters to appraise the metastatic status of formalin-fixed paraffin-embedded (FFPE) LNs. Methods: Micro-CT scans were conducted on 12 FFPEs obtained from 8 NSCLC patients with histologically confirmed mediastinal LN metastases. Simultaneously, whole-slide images from these FFPEs underwent scanning, and 47 regions of interest (ROIs) (17 metastatic foci, 11 normal lymphoid tissues, 10 adipose tissues, and 9 anthracofibrosis) were marked on scanned images. Quantitative structural variables obtained via micro-CT analysis from tumoral and non-tumoral ROIs, were analyzed. Result: Significant distinctions were observed in linear density, connectivity, connectivity density, and closed porosity between tumoral and non-tumoral ROIs, as indicated by kappa coefficients of 1, 0.90, 1, and 1, respectively. Receiver operating characteristic analysis substantiated the differentiation between tumoral and non-tumoral ROIs based on thickness, linear density, connectivity, connectivity density, and the percentage of closed porosity. Conclusions: Quantitative micro-CT parameters demonstrate the ability to distinguish between tumoral and non-tumoral regions of LNs in FFPEs. The discriminatory characteristics of these quantitative micro-CT parameters imply their potential usefulness in developing an artificial intelligence algorithm specifically designed for the 3D identification of LN metastases while preserving the FFPE tissue.

The sonographer's and pathologist's perspective of echogenic microfoci in papillary thyroid carcinoma.

Objective: Punctate echogenic foci (PEF)/microcalcifications are thought to represent psammoma bodies (PB) in histopathology. However, there are few and contradictory data on this. Different types of sonographic echogenic microfoci (EMF) are seen in papillary thyroid carcinoma (PTC), and their histopathological equivalents are not clearly known. There is also conflicting data on the interobserver agreement between the sonographers on EMF. Methods: We prospectively collected US video records of PTC nodules with and without EMF in two large thyroid centers. All video recordings were independently interpreted by three blinded, experienced sonographers. EMF were classified as true microcalcifications (punctate echogenic foci (PEF) ≤1 mm long), linear microechogenities (>1 mm long, posterior acoustic enhancement of the back wall of a microcystic area), comet-tail artifacts/reverberations or linear microechogenities with comet-tail artifacts/reverberations, non-shadowing coarse echogenic foci (>1 mm nonlinear areas) and unclassifiable. Histopathological evaluation was performed by two blinded, qualified pathologists. Results: A total of 114 malignant nodules were included. The average Cohen's kappa (κ) of three sonographers for the EMF presence was 0.775, indicating substantial agreement. A substantial agreement for PEF with 0.658 κ, only fair agreement for other types of EMF with 0.052 to 0.296 κ were detected. EMF were significantly associated with PB and papillae. PEF had an evident relationship with PB in multivariate analysis. There was a strong positive correlation between the amount of PEF and PB (r = 0.634, P < 0.001). Conclusions: PEF in PTC mainly correspond to PB on histopathology. Although observation of EMF varies among sonographers, this inconsistency can be reduced by classifying EMF into subgroups and keeping the term 'PEF' only for true microcalcifications.

The Value of Micro-CT in the Diagnosis of Lung Carcinoma: A Radio-Histopathological Perspective.

Micro-computed tomography (micro-CT) is a relatively new imaging modality and the three-dimensional (3D) images obtained via micro-CT allow researchers to collect both quantitative and qualitative information on various types of samples. Micro-CT could potentially be used to examine human diseases and several studies have been published on this topic in the last decade. In this study, the potential uses of micro-CT in understanding and evaluating lung carcinoma and the relevant studies conducted on lung and other tumors are summarized. Currently, the resolution of benchtop laboratory micro-CT units has not reached the levels that can be obtained with light microscopy, and it is not possible to detect the histopathological features (e.g., tumor type, adenocarcinoma pattern, spread through air spaces) required for lung cancer management. However, its ability to provide 3D images in any plane of section, without disturbing the integrity of the specimen, suggests that it can be used as an auxiliary technique, especially in surgical margin examination, the evaluation of tumor invasion in the entire specimen, and calculation of primary and metastatic tumor volume. Along with future developments in micro-CT technology, it can be expected that the image resolution will gradually improve, the examination time will decrease, and the relevant software will be more user friendly. As a result of these developments, micro-CT may enter pathology laboratories as an auxiliary method in the pathological evaluation of lung tumors. However, the safety, performance, and cost effectiveness of micro-CT in the areas of possible clinical application should be investigated. If micro-CT passes all these tests, it may lead to the convergence of radiology and pathology applications performed independently in separate units today, and the birth of a new type of diagnostician who has equal knowledge of the histological and radiological features of tumors.

Mitotically Active Follicular Nodule in Early Childhood: A Case Report with A Novel Mutation in the Thyroglobulin Gene.

Dyshormonogenesis is the failure of thyroid hormone production due to a defect in thyroid hormonogenesis. Loss-of-function mutations in the thyroglobulin(TG) gene are a cause of dyshormonogenesis, leading to gland stimulation by thyroid-stimulating hormone (TSH), resulting in goiter. We report a mitotically active follicular nodule in an 11-year-old female with a novel mutation in the TG gene. The patient had been under follow-up due to congenital hypothyroidism since the neonatal period, and she had normal TSH levels. Genetic test revealed a novel compound heterogeneous mutation [c.2149C>T (p.R717*) (P.Arg717Ter) / c.5361_5362delCCinsG (p.H1787Qfs*3) (p.His1787GlnfsTer3)] in TG gene. She underwent total thyroidectomy for a thyroid nodule that was reported as Bethesda IV on FNAB and noted as suspicious for noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Pathological examination revealed a 16 mm well-demarcated follicular nodule with a solid/insular pattern. Mitotic activity and Ki67 proliferation index were unusually high (10 mitoses/2mm2 and 10% respectively). Marked cellular pleomorphism and nuclear atypia are well-known diagnostic pitfalls in patients with dyshormonogenetic goiter. However, high mitotic activity is a feature that is less emphasized in dyshormonogenetic goiter and may raise suspicion of poorly differentiated carcinoma when observed together with a solid pattern. The absence of signs of invasion, history of congenital hypothyroidism, and awareness of the presence of mutations compatible with dyshormonogenetic goiter can prevent the overinterpretation of such lesions. The risk of cancer development in the dyshormonogenetic thyroid gland is possible in childhood. The close follow-up is life-saving and prevents morbidities and mortalities.

The relationship between clinicopathological parameters and PD-L1 expression level in advanced stage non-small cell lung cancer.

Introduction: Clinicopathological parameters related to programmed death ligand 1 (PD-L1) expression levels have been investigated in several studies. However, the results of these studies are conflicting and vary in different populations. This study aimed to investigate the relation of clinicopathological parameters with PD-L1 expression level in advanced stage non-small cell lung cancer patients. Materials and Methods: The patients diagnosed with non-small cell lung cancer were enrolled, retrospectively. The data of clinicopathological parameters was collected. Clinicopathological parameters in relation to PD-L1 expression levels (0%, 1-50%, and >50%) were analyzed as univariable and multivariable. Result: In total, 384 patients were enrolled. PD-L1 expression in tumor cells was between 1-50%, and >50% in 41.4%, and 23.4% of patients, respectively. There was no PD-L1 expression in 35.2% of the patients. In univariable analysis, we found that the parameters associated with PD-L1 expression levels revealed that metastatic site number, the subtype of cancer, diagnostic material type, platelet number, and LDH level were statistically significant. Adenocarcinoma frequency was higher in tumors that had PD-L1 expression >50% than in tumors that did not express PD-L1 and the difference was statistically significant (p= 0.04, coefficient= 0.3, 95% CI 0.09-0.94). Cytology as diagnostic material was significant in PD-L1 level 1-50% comparing to >50% (p= 0.02, coefficient= 2.2, 95% CI= 1.08-4.46). Conclusions: According to the results of our study, many of the clinicopathological parameters are not related to the PD-L1 level. The histological subtype and diagnostic material may affect the level of PD-L1 expression.

Operated pulmonary inflammatory myofibroblastic tumors: Our experience with 17 cases.

Background: In this study, we aimed to evaluate the clinicopathological features of pulmonary inflammatory myofibroblastic tumor cases operated in our clinic. Methods: A total of 17 inflammatory myofibroblastic tumor patients (5 males, 12 females; median age: 46 years) who were operated in our clinic between February 2000 and July 2019 were included. Data including sex, age, symptoms, accompanying diseases, tumor localization, tumor diameter, endobronchial extension, maximum standard uptake value of the tumors, surgery type, recurrence, and survival data were analyzed. Results: Two patients were diagnosed preoperatively and two patients were diagnosed during surgery using frozen-section method before resection. Three (17.7%) patients underwent pneumonectomy, five (29.4%) patients lobectomy, three (17.7%) patients segmentectomy, five (29.4%) patients wedge resection, and one (5.8%) patient bronchial sleeve resection. All patients had complete resection with negative margins. None of them had lymph node metastasis. Median follow-up was 122 (range, 8 to 245 months) months. None of the patients received adjuvant therapy, there was no tumor recurrence or tumor-related death. Conclusion: It is difficult to make a preoperative diagnosis of inflammatory myofibroblastic tumor patients. Systematic lymph node dissection is not required in diagnosed patients. Complete resection is the most important prognostic factor, and it is critical to achieve this with the smallest resection possible.

Combined clinical and specific positron emission tomography/computed tomography-based radiomic features and machine-learning model in prediction of thymoma risk groups.

OBJECTIVES: In this single-center study, we aimed to propose a machine-learning model and assess its ability with clinical data to classify low- and high-risk thymoma on fluorine-18 (18F) fluorodeoxyglucose (FDG) (18F-FDG) PET/computed tomography (CT) images. METHODS: Twenty-seven patients (14 male, 13 female; mean age: 49.6 ± 10.2 years) who underwent PET/CT to evaluate the suspected anterior mediastinal mass and histopathologically diagnosed with thymoma were included. On 18F-FDG PET/CT images, the anterior mediastinal tumor was segmented. Standardized uptake value (SUV)max, SUVmean, SUVpeak, MTV and total lesion glycolysis of primary mediastinal lesions were calculated. For texture analysis first, second, and higher-order texture features were calculated. Clinical information includes gender, age, myasthenia gravis status; serum levels of lactate dehydrogenase (LDH), alkaline phosphatase, C-reactive protein, hemoglobin, white blood cell, lymphocyte and platelet counts were included in the analysis. RESULTS: Histopathologic examination was consistent with low risk and high-risk thymoma in 15 cases and 12 cases, respectively. The age and myasthenic syndrome were statistically significant in both groups (P = 0.039 and P = 0.05, respectively). The serum LDH level was also statistically significant in both groups (450.86 ± 487.07 vs. 204.82 ± 59.04; P < 0.001). The highest AUC has been achieved with MLP Classifier (ANN) machine learning method, with a range of 0.830 then the other learning classifiers. Three features were identified to differentiate low- and high-risk thymoma for the machine learning, namely; myasthenia gravis, LDH, SHAPE_Sphericity [only for 3D ROI (nz>1)]. CONCLUSIONS: This small dataset study has proposed a machine-learning model by MLP Classifier (ANN) analysis on 18F-FDG PET/CT images, which can predict low risk and high-risk thymoma. This study also demonstrated that the combination of clinical data and specific PET/CT-based radiomic features with image variables can predict thymoma risk groups. However, these results should be supported by studies with larger dataset.

Can Radiomics Analyses in 18F-FDG PET/CT Images of Primary Breast Carcinoma Predict Hormone Receptor Status?

OBJECTIVES: This study aimed to investigate the role of preoperative 18fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) radiomics features and metabolic parameters of primary breast tumors in predicting hormone receptor (HR) positivity. METHODS: A total of 153 patients with breast carcinoma who underwent preoperative 18F-FDG PET/CT were included. All PET/CT images were retrospectively reevaluated. Radiomics features of primary breast lesions reflecting tumor heterogeneity as well as standardized uptake value (SUV) metrics (SUVmin, SUVmean, SUVmax, and SUVpeak) and volumetric parameters such as metabolic tumor volume and total lesion glycolysis (TLG) were extracted by commercial texture analysis software package (LIFEx; https://www.lifexsoft.org/ index.php). WEKA and SPSS were used for statistical analysis. Binary logistic regression analysis was used to determine texture features predicting HR positivity. Accuracy, F-measure, precision, recall, and precision-recall curve area were used as data-mining performance criteria of texture features to predict HR positivity. RESULTS: None of the radiomics parameters were significant in predicting HR status. Only SUV metrics and TLG were statistically important. Mean ± standard deviations for SUVmean, SUVmax, and SUVpeak for the HR-negative group were significantly higher than those in the HR-positive group (6.73±4.36 vs. 5.20±3.32, p=0.027; 11.55±7.42 vs. 8.63±5.23, p=0.006; and 8.37±6.81 vs. 5.72±4.86; p=0.012). Cut-off values of SUVmean, SUVmax, and SUVpeak for the prediction of HR positivity were 4.93, 8.35, and 6.02, respectively. Among data-mining methods, logistic regression showed the best performance with accuracy of 0.762. CONCLUSION: In addition to the relatively limited number of patients in this study, radiomics parameters cannot predict the HR status of primary breast cancer. SUV levels of the HR-negative group were significantly higher than those of the HR-positive group. To clarify the role of metabolic and radiomics parameters in predicting HR status in breast cancer, further studies involving a larger study population are needed.

A CT-Based Radiomic Signature for the Differentiation of Pulmonary Hamartomas from Carcinoid Tumors.

Radiomics is a new image processing technology developed in recent years. In this study, CT radiomic features are evaluated to differentiate pulmonary hamartomas (PHs) from pulmonary carcinoid tumors (PCTs). A total of 138 patients (78 PCTs and 60 PHs) were evaluated. The Radcloud platform (Huiying Medical Technology Co., Ltd., Beijing, China) was used for managing the data, clinical data, and subsequent radiomics analysis. Two hand-crafted radiomics models are prepared in this study: the first model includes the data regarding all of the patients to differentiate between the groups; the second model includes 78 PCTs and 38 PHs without signs of fat tissue. The separation of the training and validation datasets was performed randomly using an (8:2) ratio and 620 random seeds. The results revealed that the MLP method (RF) was best for PH (AUC = 0.999) and PCT (AUC = 0.999) for the first model (AUC = 0.836), and PC (AUC = 0.836) in the test set for the second model. Radiomics tumor features derived from CT images are useful to differentiate the carcinoid tumors from hamartomas with high accuracy. Radiomics features may be used to differentiate PHs from PCTs with high levels of accuracy, even without the presence of fat on the CT. Advances in knowledge: CT-based radiomic holds great promise for a more accurate preoperative diagnosis of solitary pulmonary nodules (SPNs).

HER2 Amplification by Next-Generation Sequencing in Lung Carcinoma: A Comparison of NGS Amplified and Non-amplified Cases by Immunohistochemistry and In Situ Hybridization

Background: Although the role of HER2 amplification and its evaluation methods are well known in breast carcinoma, methods for detection of HER2 amplification in non-small cell lung carcinoma are unclear. Next-generation sequencing is widely used in searching multiple therapeutic targets, and it is possible to evaluate copy number variation of genes by next-generation sequencing. Aims: To re-evaluate the HER2 status of non-small cell lung carcinoma cases detected as HER2 amplified and non-amplified by next-generation sequencing via the most commonly used HER2 investigation methods in routine pathology practice, namely immunohistochemistry and in situ hybridization. Study Design: Retrospective cross-sectional study. Methods: Among the 256 patients whose mutation profiles were examined by next-generation sequencing, HER2 amplified (13 cases) and non-HER2-amplified (13 cases) were determined as study and control groups, respectively, by next-generation sequencing. HER2 next-generation sequencing amplified tumors were investigated for HER2 expression and amplification using immunohistochemistry and silver in situ hybridization. Results: From a group of 256 non-small cell lung carcinoma, 33 tumors (12.8%) showed HER2 amplification with next-generation sequencing. Although we observed more frequent HER2 positivity by immunohistochemistry in next-generation sequencing-amplified cases, when compared to non-amplified cases (50% and 23% respectively), the difference was not significant (P = .221). Within the HER2 amplified group, inter-method-agreement was very good between next-generation sequencing results amplification and in situ hybridization status. Next-generation sequencing results showed a strong interclass correlation coefficient with HER2/cell (P = .009, r = 0.777) and HER2/CEP17 ratio (P = .001, r = 0.805). The median HER2/CEP17 ratio was higher in the next-generation sequencing amplified group (P = .013); however, three cases were found to be amplified by silver in situ hybridization among the next-generation sequencing non-amplified cases. EGFR and FGFR1 amplification were more frequent in HER2 next-generation sequencing amplified group than next-generation sequencing non-amplified group (P < .001). Conclusion: Until the effects of HER2 amplification on the HER2 protein are well understood and pulmonary carcinoma algorithms are defined, non-small cell lung carcinomas found to be amplified by next-generation sequencing should be verified by additional methods.

The role of adjuvant chemotherapy in resected stage I non - small cell lung cancer: A Turkish Oncology Group Study.

PURPOSE: The benefit of adjuvant chemotherapy for tumors smaller than 4 cm is not clear. We aimed to evaluate the prognostic impact of adjuvant platin-based chemotherapy in high-risk stage I patients with non-small cell lung cancer (NSCLC). METHODS: This cooperative group study included 232 NSCLC patients who underwent curative surgery for stage I disease with tumor size 2-4 cm. Re ults: Median age at presentation was 63 years (range 18-90). The mean tumor size was 29.6 ± 7.3 mm. The frequency of patients with specified risk factors were: visceral pleural effusion (VPI): n: 82 (36.6%); lymphovascular invasion (LVI): n: 86 (39.1%); Grade 3: n: 48 (32.7%); Solid micropapillary pattern (SMP): n: 70 (48.3%). Adjuvant platin-based chemotherapy was administered to 51 patients. During a median follow-up period of 50.5 months 68 patients (29.3%) developed recurrence, 54 (23.3%) died from any cause and 38 (16.4%) of them died of lung cancer. Patients who received chemotherapy compared with the non-chemotherapy group had a longer 5-years relapse-free survival (RFS) (84.5 vs 61.1%). Also on multivariate analysis, adjuvant chemotherapy was a significant independent prognostic factor for RFS. CONCLUSION: Adjuvant platin-based chemotherapy should be considered for patients with small tumors with adverse risk factors. Key words: adjuvant chemotherapy, lung cancer, oncology, lymphovascular invasion, solid-micropapillary pattern, platinum-based therapy.

Long-Term Outcomes of Tamoxifen Citrate Therapy and Histo- and Immunopathological Properties in Riedel Thyroiditis.

BACKGROUND: Riedel thyroiditis (RT) is a rare form of thyroiditis; thus, data about the disease course and treatment options are limited. Therefore, we aimed to assess the clinical, serological, radiological, and histopathological features, as well as short- and long-term follow-up of RT patients under glucocorticoid (GC) and tamoxifen citrate (TMX). Parameters related to IgG4-related diseases (IgG4-RD) were also investigated. METHODS: Eight patients with RT diagnosed between 2000 and 2019 were enrolled. Data were collected in a retrospective and prospective manner. The diagnosis was confirmed with histopathological features in all patients. Results of the treatment with GCs on short- to mid-term, followed by TMX in the long term, were evaluated. RESULTS: The mean age at diagnosis was 40.5 ± 6.8 years; female predominance was observed (F/M:7/1). Parameters related to IgG4-RD, like increase in IgG4 serum levels, total plasmablast counts, and IgG4+ plasmablasts, were negative in most of our patients in both active and inactive states of the disease. Likewise, an increased ratio of IgG4/IgG-positive plasma cells >40% could only be observed in 2 cases. GCs followed by TMX were given to the patients with an over-all median follow-up time of 67 (8-216) months. All the patients considerably improved clinically and had a reduction in the size of the mass lesion on GCs, followed by TMX therapy. None of the patients had a recurrence under TMX therapy for a median period of 18.5 (7-96) months. CONCLUSION: Even though RT is suggested to be a member of IgG4-RD, serologic or histological evidence of IgG4 elevation or positivity is only useful for diagnosis and follow-up of RT. The diagnosis should be based on clinical and radiological evidence and confirmed by histopathology. GCs are effective for initial treatment, and TMX is a successful and safe therapeutic option for long-term maintenance therapy.

The prognostic value of 18F-fluorodeoxyglucose positron emission tomography/ computed tomography parameters in patients with malignant pleural mesothelioma.

BACKGROUND: In this study, we aimed to investigate the prognostic value of metabolic 18F-fluorodeoxyglucose positron emission tomography/computed tomography parameters in malignant pleural mesothelioma patients. METHODS: A total of 65 patients with malignant pleural mesothelioma (34 males, 31 females; median age: 60 years; range, 39 to 84 years) who underwent whole-body 18F-fluorodeoxyglucose positron emission tomography/computed tomography for staging before treatment between March 2008 and January 2018 were included. Relationships between clinicopathological factors and 18F-fluorodeoxyglucose positron emission tomography/computed tomography parameters and overall survival were evaluated using a log-rank test and Cox regression analysis. RESULTS: The median follow-up was 13 (range, 4 to 55) months. The Kaplan-Meier analysis revealed a mean survival time of 17±2.6 months. The cumulative two- and five-year survival rates were 34.8% and 7.8%, respectively. Univariate analysis showed that ≥60 age, left hemithorax involvement, a maximum standardized uptake value of ≥9.8, c-T4 status, c-M1 status, and non-surgery were negatively associated with overall survival (p<0.05). Multivariate analysis showed that ≥60 age, left hemithorax involvement, a maximum standardized uptake value of ≥9.8, c-M1 status, and a total lesion glycolysis of ≥180.2 g were negatively associated with overall survival (p<0.05). CONCLUSION: Metabolic parameters of 18F-fluorodeoxyglucose positron emission tomography/computed tomography have the potential to provide prognostic information for malignant pleural mesothelioma patients who are receiving surgery and/or chemotherapy.

Differentiation of benign and malignant regions in paraffin embedded tissue blocks of pulmonary adenocarcinoma using micro CT scanning of paraffin tissue blocks: a pilot study for method validation.

PURPOSE: Micro computed tomography (micro-CT) can provide detailed information about the internal structure of materials. This study aimed to demonstrate the diagnostic value of micro-CT in formalin fixed paraffin embedded pulmonary adenocarcinomas by correlating the micro-CT findings of tumoral and non-tumoral areas with hematoxylin and eosin (HE) sections. METHODS: Paraffin blocks obtained from three adenocarcinomas were scanned with micro-CT. Ten regions of interest (ROIs) from adenocarcinoma and 11 ROIs from pulmonary parenchyma (ROI-C and ROI-N, respectively) areas were compared regarding the various structural parameters. RESULTS: All parameters were significantly different regarding the tumoral and non-tumoral ROIs. The percent object volume, structure thickness, structure linear density, connectivity and connectivity density were higher in ROI-Cs (p < 0.000, p < 0.000, p = 0.001, p < 0.000, and p < 0.000 respectively); whereas intersection surface and structure model index were higher in ROI-Ns (p < 0.000 and p < 0.000). The open porosity percentage was higher in ROI-Ns (68.86 + 2.96 vs 48.29 + 5.11, p < 0.000) and the closed porosity percentage was higher in ROI-Cs (2.29 + 0.55 vs 0.57 + 0.17 p < 0.000). CONCLUSIONS: The tumoral and non-tumoral areas in paraffin blocks can be distinguished from each other, using the quantitative and qualitative information obtained by micro-CT. Making this distinction with quantitative data obtained from micro-CT can therefore be the basis of creating artificial intelligence algorithms in the future.

Capsular Invasion Matters Also in "Papillary Patterned" Tumors: A Study on 121 Cases of Encapsulated Conventional Variant of Papillary Thyroid Carcinoma.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid malignancy. Some PTCs with classical papillae can be totally or partially encapsulated, and these tumors are called "encapsulated" (conventional) variant of papillary thyroid carcinoma. We aimed to investigate the clinicopathological features of this variant, comparing with non-encapsulated conventional type PTC. Among 823 thyroidectomy specimens with PTC diagnosed between 2015 and 2018, 121 tumors from 105 patients (12.75%) were reclassified as encapsulated conventional PTC. In 76 patients, tumors were unifocal. Size, cystic changes, background thyroiditis, psammoma bodies, cervical lymph node metastasis at presentation, capsular/vascular invasion, and immunohistochemical BRAF-V600E expression were evaluated. Ninety-two non-encapsulated conventional PTCs served as control group. Encapsulated cases were predominantly women (73.3%), 56.4% were microcarcinomas, 97.5% had cystic changes, 81.4% were BRAF-V600E positive, and 36.8% of unifocal encapsulated tumors had cervical lymph node metastasis. Thyroiditis and psammoma bodies were detected in nearly half of the encapsulated PTCs. Fourteen percent of the unifocal tumors showed total encapsulation, whereas capsular and vascular invasion was detected in 85.5% and 5.8%, respectively. Encapsulated cases did not show any significant difference from the control group, except for prominent cystic changes (p < 0.001). Relationship between lymph node metastasis at presentation and capsular invasion was statistically significant (p = 0.001), and metastasis was more frequent in cases with extensive capsular invasion (no/minimal invasion versus extensive invasion, p < 0.001). Cystic changes are very common, and this feature deserves mentioning as a morphological characteristic of encapsulated conventional PTCs. As in encapsulated "follicular" variant of PTC, capsular invasion status is important in evaluating papillary patterned encapsulated PTC for predicting lymph node metastasis. Total examination of the tumor capsule and inclusion of capsular invasion status in pathology reports are recommended.

Primary pulmonary paraganglioma: Two cases.

Paraganglioma is a rare tumor originating from extra-adrenal chromaffin cells. Primary pulmonary paraganglioma can also be seen in pediatric patients. Due to its endobronchial localization, morphological features, and neuroendocrine immunohistochemical profile, primary pulmonary paraganglioma can be confused with carcinoid tumor. Primary pulmonary paraganglioma should be considered in the differential diagnosis of endobronchial tumors and necessary precautions should be taken, considering that it may be functioning. In appropriate cases, bronchial sleeve resection provides curative treatment. In this article, we present two cases: First was a functioning primary pulmonary paraganglioma that underwent lobectomy and second was an entirely endobronchial tumor without any extra-bronchial spread that underwent bronchial sleeve resection.

Study of mouse induced pluripotent stem cell transplantation intoWistar albino rat cochleae after hair cell damage.

BACKGROUND/AIM: As the regeneration capacity of hair cells is limited, inner ear stem cell therapies hold promise. Effects of mouse induced pluripotent stem cells (IPSCs) on Wistar albino rats (WARs) with hearing impairment were investigated. MATERIALS AND METHODS: Thirty-five adult WARs with normal hearing were divided into 4 groups. Excluding the study group (n = 15), the other three groups served as control groups for ototoxicity and IPSC injection models. IPSC injections were performed via cochleostomy after a retroauricular approach. Auditory functions were evaluated with auditory brainstem responses (ABRs) before and after the injections. After a final hearing assessment the WARs were sacrificed and cochleae were extracted to see the biologic behavior of IPSCs in the inner ear by light microscopy and immunohistochemistry. RESULTS: There were no significant differences in the click-ABR thresholds in the study group after IPSC transplantation. The mean hearing threshold in the study group after ototoxic agent injection was 53.2 dB (10-90 dB). There was no significant difference between groups (P > 0.05) and no differentiated stem cells were observed immunohistochemically. CONCLUSION: Transplanted IPSCs did not show a therapeutic effect in this trial. We discuss potential pitfalls and factors affecting the therapeutic effect.

Diffuse Neuroendocrine Cell Hyperplasia: Report of Two Cases.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare pulmonary disorder characterised by a proliferation of neuroendocrine cells within the lung. It is believed that a minority of the patients with DIPNECH can develop carcinoid tumors. Here, we report two new cases of DIPNECH with coexisting carcinoid tumors.

Cervical Paraganglioma Mimicking Thyroid Nodule: A Rare Clinical Case.

Objective. Paraganglioma is a rare neuroendocrine tumor. When it is located in the neck, it is commonly misdiagnosed as other thyroid neoplasms. Case Report. We report a case of cervical paraganglioma in a 55-year-old female. Patient was admitted to our clinic with goiter and neck pain. Thyroid ultrasonography revealed a 20 mm solitary, heterogeneous nodule located in the upper pole of left thyroid lobe. Fine needle aspiration cytology was nondiagnostic. She underwent left lobectomy and histopathology showed paraganglioma. Discussion. Cervical paragangliomas should be considered in the differential diagnosis of thyroid nodules.