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Background: Recent studies have shown a lower likelihood of locoregional recurrences in patients with low 21-gene recurrence score (RS). In this single institutional study, we investigated any associations between different cut-off values of 21-gene RS and histopathological factors and outcome in patients with long-term follow-up. Methods: Between February 2010 to February 2013, 61 patients with early stage clinically node-negative hormone receptor-positive and HER2-negative breast cancer tested for the 21-gene RS assay, were included into the study. The clinicopathological, treatment and outcome characteristics were analyzed. Results: Median age was 48 (range, 29-72). Of those, 53 patients were diagnosed with Stage 1 (86.9%) and 8 patients were Stage 2 (13.1%) following surgery. Patients with high histologic grade (HG), or with Ki-67>=25% were significantly more likely to have intermediate/high RS based on RS >11 and >18 (Table 1). Based on the 21-gene RS assay, only 19 patients (31%) received adjuvant chemotherapy. At a median follow-up of 112 months, 3 patients developed local recurrences (4.9%) treated with endocrine therapy alone. Among patients treated with endocrine treatment alone (n=42), the clinicopathological characteristics including age < 40, age < 50, high histologic or nuclear grade, high Ki67-scores (>=20%, >=25%, >=30%), presence of lymphovascular invasion, luminal-A type tumor, multifocality, lymph node positivity, tumor size more than 2 cm, RS>=18 or RS>11 were not significantly found to be associated with 10-year locoregional recurrence free survival (LRRFS). However, patients with a RS >=16 have significantly shown a poorer 10-year LRRFS cpmpared to those with RS < 16 (RS < 16; 100% vs RS>=16; 75%, p=0.039, Table 2). Conclusions: These results suggest that Oncotype DX assay may be of little value in patients with high histologic grade or high Ki67 scores (>= 25%) as treatment decision criteria to determine any benefit from chemotherapy. Furthermore, patients with a RS >=16 are more likely to benefit from adjuvant chemotherapies, whereas those with a RS < 16 have an excellent outcome and local control on long term follow-up with endocrine treatment alone. Further prospective studies should be performed to validate these findings in future. Table 1. Correlation of 21-gene Recurrence Score (RS) including different cut-off values with Ki-67 scores and histopathological factors Table 2. Clinicopathologic factors and 21-gene Recurrence Score (=RS) associated with disease free survival (DFS) and locoregional recurrence free survival free survival (=LRRFS). (DFS is equal to LRRFS since none of the patients developed distant metastases) Citation Format: Cihan Uras, Neslihan Cabıoğlu, Fatma Tokat, Halil Kara, Ozlem ER, Taner Korkmaz, Nuran Bese, Umit Ince. FAVORABLE LOCOREGIONAL CONTROL IN CLINICALLY NODE-NEGATIVE HORMONE-RECEPTOR POSITIVE BREAST CANCER WITH LOW 21-GENE RECURRENCE SCORES: A SINGLE INSTITUTIONAL STUDY WITH 10-YEAR FOLLOW-UP [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-31.

Objective: Vascular endothelial growth factor (VEGF) is an angiogenic factor that plays an important role in physiological and pathological angiogenesis of the thyroid. The aim of the current study was to determine the expression characteristics of VEGF in follicular cell-derived lesions of the thyroid and to assess whether a new entity noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is precancerous. Material and Methods: Patients diagnosed with 33 follicular adenomas (FA), 41 invasive follicular variant papillary thyroid cancer (IN-FVPTC), and 40 NIFTP in surgical resection materials were evaluated retrospectively. Immunostaining was performed on 5-μm paraffin tissue sections. The percentages of immunostaing for VEGF were evaluated on pathological materials. We used a percentage of labeled thyrocytes score (0, no labeling; 1, 60%) and an intensity score (0, no staining; 1, weak; 2, intermediate; 3, strong). The sum of two scores were accepted as the total score. Results: Mean ages of the FA, IN-FVPTC, and NIFTP groups were 44.7 ± 11.7 years, 46.9 ± 13.6 years, 43.2 ± 15.4 years, respectively and the mean VEGF immunostaining scores were 44.7 ± 29.3, 50.2 ± 32.54, 4 ± 26.3 respectively. Although there was no statistically significant difference (p= 0.347), the total score of the NIFTPs was higher than the scores of the FA (mean= 3.9 ± 1.8) and IN-FVPTC(mean= 4.3 ± 1.9) groups with a mean value of 4.6 ± 1.7. This result was remarkable. There was no statistically significant difference between tumor diameters and staining percentages (p= 0.750). Conclusion: Even if there were no statistical differences for VEGF immunostaining, it was high in NIFTPs. Since we know the role of VEGF in tumorigenesis, we can hypothesize that NIPTP can be precancerous. Our argue should be corroborated by a large prospective study.

The tubule index is a vital prognostic measure in breast cancer tumor grading and is visually evaluated by pathologists. In this paper, a computer-aided patch-based deep learning tubule segmentation framework, named Tubule-U-Net, is developed and proposed to segment tubules in Whole Slide Images (WSI) of breast cancer. Moreover, this paper presents a new tubule segmentation dataset consisting of 30820 polygonal annotated tubules in 8225 patches. The Tubule-U-Net framework first uses a patch enhancement technique such as reflection or mirror padding and then employs an asymmetric encoder-decoder semantic segmentation model. The encoder is developed in the model by various deep learning architectures such as EfficientNetB3, ResNet34, and DenseNet161, whereas the decoder is similar to U-Net. Thus, three different models are obtained, which are EfficientNetB3-U-Net, ResNet34-U-Net, and DenseNet161-U-Net. The proposed framework with three different models, U-Net, U-Net++, and Trans-U-Net segmentation methods are trained on the created dataset and tested on five different WSIs. The experimental results demonstrate that the proposed framework with the EfficientNetB3 model trained on patches obtained using the reflection padding and tested on patches with overlapping provides the best segmentation results on the test data and achieves 95.33%, 93.74%, and 90.02%, dice, recall, and specificity scores, respectively.

Carcinoma showing thymus-like differentiation (CASTLE) is a rare neoplasm of the thyroid or the adjacent tissues in the neck. It was first described by Miyauchi et al. in 1985 as an intrathyroidal epithelial thymoma. In 1991 Chan and Rosai classified these tumors into four types including CASTLE. World Health Organization (WHO) declared it as an independent clinicopathologic entity in 2004. The tumor arises from ectopic thymus tissue or remnants of branchial pouch. Both sexes are affected similarly with a slight female dominance. It is usually encountered in the fourth and fifth decades of life. It does not have specific symptoms or radiologic findings which makes preoperative diagnosis difficult. It has a higher tendency to be located in the lower poles of thyroid lobes. Immunohistochemistry helps differentiate it from other malignant neoplasms, CD5 being an important marker. The tumor is negative for thyroid specific markers as thyroglobulin, TTF-1 or calcitonin. Surgery is considered the mainstream therapy. Radiotherapy may be reserved for gross disease or recurrence. The role of chemotherapy is unclear. The prognosis of CASTLE is favourable.

Background The progression to gastric cancer has been linked to chronic infection with Helicobacter pylori (H. pylori). Immune checkpoint inhibitors (programmed cell death -1, PD-1; programmed cell death –ligand 1, PD-L1) have a role in cancer immune escape. The relationship between H. pylori virulence factors with PD-1, PD-L1 T helper 1 (Th1), T helper 17 (Th17), and regulatory T cell (Treg) response genes, has not been thoroughly investigated in the development of gastric cancer. Therefore, we evaluated how H. pylori virulence factors influence the expression levels of immune-related genes in the development of gastric immunopathology. Methods A total of 92 gastric tissues of normal controls and patients with gastritis, gastric ulcer, and gastric cancer were examined for the expression of immune-checkpoint inhibitor genes (PD-1 PD-L1), Th1 (interferon- γ, IFN-γ), Th17 (interleukin- 17, IL-17, Retinoic-acid-receptor- related orphan nuclear receptor gamma t, RORγ-t), and Treg (Forkhead box P3, FOXP3) response genes with quantitative real-time PCR (qRT-PCR). Furthermore, correlation of H. pylori virulence factors’ (cytotoxin-associated gene A, cagA; vacuolating cytotoxin gene A, vacA (s1,s2,m1,m2); blood group antigen-binding adhesin gene A, babA, duodenal ulcer promoting gene A, dupA; the putative neuraminyllactose-binding hemagglutinin homolog, hpaA; neutrophil-activating protein A napA; outer inflammatory protein A, oipA; urease A, ureA; and urease B, ureB) genotypes with a degree of inflammation and density of H. pylori were investigated. Next, the relationship between H. pylori virulence factors and immune-checkpoint inhibitor genes, and T-cell response genes was evaluated. Eventually, a decision tree model was developed to determine the clinical outcome of patients using expression data. Results The intensity of PD-1 and PD-L1 mRNA expression was increased significantly in gastric tissue of patients with gastric ulcer (PD-1: 2.3 fold, p=0.01; PD-L1: 2.1 fold, p=0.004), and gastric cancer (PD-1: 2 fold, p= 0.04; PD-L1: 1.8 fold, p=0.05) compared with control subjects. Also, PD-1: PD-L1 expression was significantly higher in patients with gastritis, who were infected with a marked density of H. pylori compared with its mildly infected counterparts. Furthermore, a novel negative correlation was found between PD-1 (r= -0.43) and PD-L1 (r= -0.42) with FOXP3 in patients with gastritis. CagA-positive H. pylori strain's negative association with PD-L1 expression (r=-0.34) was detected in patients with gastritis. Interestingly, PD-1 mRNA expression correlated positively with vacA s2/m2, in gastritis (r=0.43) and ulcer (r=0.43) patients. Furthermore, PD-1: PDL1 expression negatively correlated with vacA m1/m2 (r=-0.43 for PD-1; r=-0.38 for PD-L1) in gastritis patients. Moreover, an inverse correlation of PDL1 was present with vacA m1 (r=0.52) and vacA s1/m1 (r=0.46) versus vacA m2 (r=-0.44) and vacA m1 (r=0.52) and vacA s1/m2 (r=-0.14) in ulcer patients, respectively. Also, a correlation of vacA m2 (r=-0.47) and vacA s1/s2 (r= 0.45) with PD-1 was detected in ulcer patients. In addition, a novel negative correlation between FOXP3 mRNA levels and napA was shown in patients with gastritis and ulcer (r=-0.59). Finally, a computer-based model that was developed showed that knowing the expression levels of PD-L1, RORγ-t, and vacA s1/m2 would be useful to detect the clinical outcome of a patient. Conclusion Our results suggested that PD-1:PD-L1 immune checkpoint inhibitors were increased in gastric pre-cancerous lesions that progress to gastric cancer. Herein, we report the relationship between H. pylori virulence factors and expression of host immune checkpoint inhibitors for diagnostic prediction of gastric malignancies using computer-based models.

Sporcularda performansı belirleyen fiziksel, fizyolojik, psikolojik ya da çevresel birçok faktör vardır. Günümüzde bu faktörlerin tek başına değil birbiriyle etkileşim halinde ve birbirini tamamlayarak kişinin performansını etkilediği bilinmektedir. Bu faktörlerden, aerobik-anaerobik dayanıklılık ve zihinsel dayanıklılık becerileri de kimi araştırmacılara göre birbiriyle ilişkili, kimilerine göre ise ilişkili değildir. Bu bağlamda çalışmamızın amacı, spor bilimleri fakültesi öğrencilerinin anaerobik dayanıklılık ile zihinsel dayanıklılık düzeyleri arasında ilişki olup olmadığının tespit edilmesidir. Araştırmamıza Gazi Üniversitesi Spor Bilimleri Fakültesi öğrencilerinden 18-29 yaş arası 68 erkek, 52 kadın olmak üzere 120 sporcu öğrenci katılmıştır. Demografik bilgi formunda cinsiyet ve spor yaşına ilişkin sorulara yer verilmiştir Sheard, Golby & Van Wersch (2009) tarafından geliştirilen, Türkçe uyarlaması Altıntaş & Koruç Bayar (2016) tarafından gerçekleştirilen Sporda Zihinsel Dayanıklılık Envanteri (SZDE) kullanılmıştır. Bisiklet ergometresinde 30 saniye süre ile vücut ağırlığına göre yüke karşı (%7,5) maksimum hızda pedal çevirmeye dayanan Wingate Anaerobik Güç testi uygulanmıştır. Veriler Spss 25 kullanılarak 0,05 düzeyinde anlamlılıkta analiz edilmiştir. Verilerin Shapiro-Wilk testi ile normal dağılım gösterdiği tespit edilmiştir. Değişkenler arasındaki ilişkiyi belirlemek için pearson korelasyon analizi uygulanmıştır. Cinsiyete göre ve cinsiyet göz ardı edildiğinde tüm katılımcılarda zihinsel dayanıklılık ve anaerobik dayanıklılık verileri arasında farklılık görülmemiştir (p>.05). Zihinsel dayanıklılık ve anaerobik dayanıklılık verileri arasında ilişki tespit edilmemiştir (p>.05). Sporcularda zihinsel dayanıklılık ve fiziksel dayanıklılığı doğrudan ilişkili olduğunu ya da ilişkisiz olduğunu belirtmek çok mümkün değildir. Deneysel yöntemlerle yürütülen çalışmalarda ilişki tespit edilirken, betimsel yöntemlerle yürütülen çalışmalarda genelde ilişki tespit edilememektedir. Sonuçta betimsel tarama yöntemiyle yapılan çalışmamızda da ilişki olmadığı görülmüştür.

The current study seeks to investigate the link between mindfulness, static and dynamic balance among elite athletes. 77 elite athletes (Mage=19.03 years, SD = 3.00) completed a Demographic Information Form and the Mindfulness Inventory for Sport. In addition, Y Balance Test and Flamingo Test were used for balance measurements. Simple correlation analysis indicated that overall mindfulness was not significantly related to dynamic and static balance. However, the awareness subscale of mindfulness was negatively correlated with dynamic balance. In addition, the results of the regression showed that the awareness subscale of mindfulness significantly predicted dynamic balance. Findings suggest that awareness, albeit low, may be an important predictor of dynamic balance in elite athletes.

Background: Recent studies have shown a lower likelihood of locoregional recurrences in patients with low 21-gene recurrence score (RS). In this single institutional study, we investigated any associations between different cut-off values of 21-gene RS and histopathological factors and outcome in patients with long-term follow-up. Methods: Between February 2010 to February 2013, 61 patients with early stage clinically node-negative hormone receptor-positive and HER2-negative breast cancer tested for the 21-gene RS assay, were included into the study. Demographic, clinicopathological, treatment and outcome characteristics were analyzed.Results: Median age was 48 (range, 29-72). Of those, 53 patients were diagnosed with Stage 1 (86.9%) and 8 patients were Stage 2 (13.1%) following surgery. Patients with high histologic grade (HG), or with Ki-67>25%were more likely to have intermediate/high RS based on RS >11 and >18. Based on the 21-gene RS assay, only 19 patients (31%) received adjuvant chemotherapy. At a median follow-up of 112 months, 3 patients developed local recurrences (4.9%) treated with endocrine therapy alone. Among patients treated with endocrine treatment alone (n=42), the clinicopathological characteristics including age >20%, >25%, >30%), presence of lymphovascular invasion, luminal-A type, multifocality, lymph node positivity, tumor size more than 2 cm, RS>18 or RS>11 were not significantly found to be associated with 10-year locoregional recurrence free survival (LRRFS). However, patients with a RS >16 have significantly shown a poorer 10-year LRRFS compared to those with RS >16; 75%, p=0.039). Conclusions: These results suggest that Oncotpe DX assay may be of little value in patients with high histologic grade or high Ki67 scores (>25%) as treatment decision criteria to determine any benefit from chemotherapy. Furthermore, patients with a RS >16 are more likely to benefit from adjuvant chemotherapies, whereas those with a RS

Background Signs of inflammation including epidermal interface changes, spongiosis and dermal inflammation as well as pagetoid dyskeratosis are rarely described in fibrous papule (FP). We aimed to describe the inflammatory parameters, the rate of pagetoid dyskeratosis, along with CD163 immunohistochemical staining as an adjunctive diagnostic tool in FP. Methods Histopathology samples of all biopsy-proven FP cases were retrieved from archives and investigated for inflammatory parameters, presence of pagetoid dyskeratosis, as well as CD163, CD10 and CD34 immunostaining pattern of dermal spindle/stellate or multinucleate cells (graded from 0 to 4). Results Thirty-two cases of FP were identified. A high rate of inflammatory parameters including interface changes (20/32), spongiosis (31/32), and dermal lymphocytic inflammation (31/32) were detected. Pagetoid dyskeratosis was identified in eight out of 32 cases (25%). A grade 4 staining revealing a strong dendritic pattern was confirmed in all FP cases with CD163 immunohistochemistry including atypical variants such as granular FP, compared with CD10 (11/32) and CD34 (3/32). Conclusion The dendritic cellular proliferation in FP may represent an inflammatory response to various stimuli; pagetoid dyskeratosis is a relatively common and underrecognized epidermal feature and CD163 immunostaining may be used as an adjunctive diagnostic tool in unusual histopathological subtypes. This article is protected by copyright. All rights reserved.

Morton’s neuroma is a mechanical neuropathy of plantar interdigital nerve. It is one of the most common causes of forefoot pain. One of the most undesirable complications of Morton’s neuroma surgery is recurrent neuroma. Excision level of Morton’s neuroma is important to prevent recurrence. In this study, we aimed to figure out preferred excision levels of orthopedic surgeons by evaluating pathological samples. Pathological specimens of 192 patients were prepared and examined by the same pathologist. One hundred thirty-nine patients were women (72.3%) and 53 were men (27.6%). The most common interspace affected was the third at 171 (89%) patients, followed by the second at 21 (11%). Mean age was 45.8 years (between 23 and 73). Twenty-two of them were left foot and the other 170 were right foot. Recurrent neuromas, pathological sample more than one piece from one surgical site, were excluded from the study. Pathological specimens were prepared and examined by the same pathologist. Gross pathological appearance and histopathological findings were recorded. Mean sample length was 2.05 cm (between 0.8 and 6 cm). One hundred forty-five samples were smaller (75.5%) than 3 cm, and only 47 samples (24.5%) were bigger than 3 cm. Our database results showed that majority of surgeons excise the nerve shorter than it should be. One of the reasons for high recurrence rates in Morton neurinoma may be inadequate excision of the nerve.

AIM To determine whether performing incision on the surface of the ovarian cortex in rats advances follicular development. METHODS Five to seven separate superficial incisions were performed on the surface of right ovaries of 6-7-month-old albino Wistar rats. Daily 40 IU of gonadotropins were administered for 14 days. On the 15th day, both ovaries of the rats were removed. The right (incised) ovaries were compared with the contralateral ovaries in terms of ovary's weight, numbers of primordial, primary, secondary and antral follicles, their mean percentages and mean Ki-67 proliferation indices. RESULTS A total of 22 ovaries were evaluated, with 11 right ovaries (incised) and 11 left ovaries (non-incised). The mean weight of ovaries was greater in the right ovaries than in the left ovaries; however, no statistical difference was found between them (0.77 ± 1.22 vs. 0.22 ± 0.08 gr, P = 0.159). The numbers of secondary and antral follicle were statistically higher in the right ovaries than in the left ovaries (4.4 ± 1.5 vs. 2.1 ± 1.6, P = 0.003 and 18.6 ± 8.7 vs. 11.3 ± 7.5, P = 0.046, respectively). The right ovaries also significantly differed from the left ovaries in terms of mean percentages of primordial and antral follicles (P

BackgroundThis study investigates the effects of COVID-19 on the breast cancer stage and the volume of breast cancer surgery in a specialized breast institute.MethodsData of 332 patients who were diagnosed and treated for breast cancer between December 2019 and November 2020 were evaluated retrospectively according to periods of pandemic.ResultsA significant decrease in the number of operations, especially upfront surgeries rather than surgeries after neoadjuvant chemotherapy, was detected in the early period of the COVID-19 pandemic. It was found that patients with complaints were mostly admitted during this period (p = 0.024). No statistical significance was found for age, sex, side of the tumor, type of tumor, surgery to breast, and axilla. Following the early period of the pandemic, it was observed that patients with mostly luminal, early-stage, and less axillary nodal involvement (p < 0.05) were admitted, and as a result, it was founded that upfront surgeries increased, although no change in TNM staging was observed. However, it did affect the decision of initial treatment. Thus, the number of upfront surgeries was significantly higher than the NCT group (p = 0.027) following the early period.ConclusionSurgical volume is significantly affected in the early period of the COVID-19 pandemic. To overcome overload due to delayed surgeries related to pandemics, some hospitals should be spared for oncological treatments. Following the early period, mostly luminal type, early-stage patients were admitted, probably because of increased self-awareness and short wave duration, but the breast cancer stage was not affected.

e13607 Background: The Nottingham histologic grade (NHG) is a strong prognostic factor in early-stage breast cancer. It consists of nuclear pleomorphism, tubular formation, and mitotic count. We recently developed an artificial intelligence (AI) based automatic grading system. Methods: In this study, we have retrospectively evaluated 179,651 hematoxylin and eosin-stained patches extracted from 402 digitized biopsies of 338 patients with confirmed invasive ductal carcinoma diagnosis. The data was collected at Acıbadem University Hospital between 2017 and 2021. The digitized slides were manually labeled by seven pathologists before being used to train the deep learning models (DL). The pre-trained (on ImageNet) DL architectures which are EfficientNet backbone U-Net, YOLOv5, DenseNet161, and a modified VGG-11 have been fine-tuned with this study’s dataset for the tubule segmentation, nuclei detection, mitosis classification, and the nuclear pleomorphism classification tasks, respectively. Data augmentation for boosting the accuracy was done. Semantic segmentation for tubular formation, object detection for detection of nuclei, and image classification for the mitotic count and nuclear pleomorphism was also performed. Results: The AI-based algorithms have obtained reproducible histologic scores with mean F1 scores, sensitivities, and specificities as presented in Table. Conclusions: The AI-based automatic grading system is accurate in the evaluation of the components of NHG. This system will speed up the pathology workflow in the clinic, provide decision support to pathologists and mitigate the sensitivity associated with the traditional grading process. [Table: see text]

Background Recent studies have shown a lower likelihood of locoregional recurrences in patients with a low 21-gene recurrence score (RS). In this single-institution study, we investigated whether there are any associations between different cutoff values of 21-gene RS, histopathological factors, and outcome in patients with long-term follow-up. Methods The study included 61 patients who had early-stage (I-II) clinically node-negative hormone receptor-positive and HER2-negative breast cancer and were tested with the 21-gene RS assay between February 2010 and February 2013. Demographic, clinicopathological, treatment, and outcome characteristics were analyzed. Results The median age was 48 years (range, 29–72 years). Patients with high histologic grade (HG), Ki-67 ≥ 25%, or Ki-67 ≥ 30% were more likely to have intermediate/high RS (≥ 18). Based on the 21-gene RS assay, only 19 patients (31%) received adjuvant chemotherapy. At a median follow-up of 112 months, 3 patients developed locoregional recurrences (4.9%), which were treated with endocrine therapy alone. Among patients treated with endocrine treatment alone (n = 42), the following clinicopathological characteristics were not found to be significantly associated with 10-year locoregional recurrence free survival (LRRFS): age 11. However, patients with RS ≥ 16 had significantly poorer 10-year LRRFS compared to those with RS p = 0.039). Conclusions The results suggest that patients with clinically node-negative disease and RS ≥ 16 are more likely to benefit from adjuvant chemotherapies. However, those with RS

Mitosis assessment of breast cancer has a strong prognostic importance and is visually evaluated by pathologists. The inter, and intra-observer variability of this assessment is high. In this paper, a two-stage deep learning approach, named MITNET, has been applied to automatically detect nucleus and classify mitoses in whole slide images (WSI) of breast cancer. Moreover, this paper introduces two new datasets. The first dataset is used to detect the nucleus in the WSIs, which contains 139,124 annotated nuclei in 1749 patches extracted from 115 WSIs of breast cancer tissue, and the second dataset consists of 4908 mitotic cells and 4908 non-mitotic cells image samples extracted from 214 WSIs which is used for mitosis classification. The created datasets are used to train the MITNET network, which consists of two deep learning architectures, called MITNET-det and MITNET-rec, respectively, to isolate nuclei cells and identify the mitoses in WSIs. In MITNET-det architecture, to extract features from nucleus images and fuse them, CSPDarknet and Path Aggregation Network (PANet) are used, respectively, and then, a detection strategy using You Look Only Once (scaled-YOLOv4) is employed to detect nucleus at three different scales. In the classification part, the detected isolated nucleus images are passed through proposed MITNET-rec deep learning architecture, to identify the mitosis in the WSIs. Various deep learning classifiers and the proposed classifier are trained with a publicly available mitosis datasets (MIDOG and ATYPIA) and then, validated over our created dataset. The results verify that deep learning-based classifiers trained on MIDOG and ATYPIA have difficulties to recognize mitosis on our dataset which shows that the created mitosis dataset has unique features and characteristics. Besides this, the proposed classifier outperforms the state-of-the-art classifiers significantly and achieves a $$68.7\%$$ 68.7 % F1-score and $$49.0\%$$ 49.0 % F1-score on the MIDOG and the created mitosis datasets, respectively. Moreover, the experimental results reveal that the overall proposed MITNET framework detects the nucleus in WSIs with high detection rates and recognizes the mitotic cells in WSI with high F1-score which leads to the improvement of the accuracy of pathologists’ decision.

Rationale and Objectives: Adenoid cystic carcinoma (ACC) of the breast is a rare type of breast cancer with favorable prognosis. There is limited data on the radiological findings of this rare tumor in literature. The aim of this study is to determine the most common imaging features and review the literature. Materials and Methods: Pathological databases of seven institutions from 2009 to 2021 were retrospectively reviewed, and patients with a diagnosis of ACC of the breast were determined. Thirteen patients whose imaging studies could be recalled from the picture archiving systems (PACS) were included in the study. Clinical and pathological findings as well as follow-up data were recorded. Radiological findings were analyzed and categorized based on BI-RADS 5th edition. Results: There were 16 mass lesions in 13 patients (two multifocal cases, one case with recurrence). Mammography demonstrated 14 masses, while ultrasound (US) demonstrated all. MRI was available in only seven cases, with eight masses. The most common findings were round or oval shape on all modalities (78.57%–93.75%). Other frequent findings were parallel orientation (81.25%), isoechoic or hyperechoic echogenicity (62.5%), high T2 signal (87.5%), restricted diffusion (71.43%), and homogeneous enhancement (62.5%). Mammography, US and MRI showed circumscribed margins resembling a benign lesion in 35.71%, 37.5% and 50% of the lesions respectively. Three patients had a cyst-like echogenicty on US. Half of the lesions were avascular on Doppler US (6/12) and half were soft (2/4) on strain elastography. Although there were benign features on all imaging modalities seperately, all lesions could be categorized as BI-RADS 4 or 5 when the findings were combined. However 9/16 masses were BI-RADS 4A, emphasizing the subtlety of the malignant features. Conclusion: ACC of the breast can present with findings resembling a benign lesion on different imaging modalities. Although combination of all imaging findings correctly indicated the suspicious nature of the lesions in all cases, final classification was BI-RADS 4A in most of them. Radiologists should be aware of the more frequent findings of ACC of the breast for early diagnosis. US findings of isoechoic or hyperechoic appearance, and cyst-like echogenicity have not been reported previously in literature. © 2022 The Association of University Radiologists

Emel Öztürk Durmaz,1 Deniz Demircio&gbreve;lu,1 P&inodot;nar Yal&inodot;nay Dikmen,2 Yasemin Alanay,3 Ahmet Alanay,4 Cüyan Demirkesen,5 Fatma Tokat,5 Ercan Karaarslan6 1Department of Dermatology, Ac&inodot;badem Mehmet Ali Ayd&inodot;nlar University School of Medicine, &Idot;stanbul, Turkey; 2Department of Neurology, Ac&inodot;badem Mehmet Ali Ayd&inodot;nlar University School of Medicine, &Idot;stanbul, Turkey; 3Department of Pediatrics, Ac&inodot;badem Mehmet Ali Ayd&inodot;nlar University School of Medicine, &Idot;stanbul, Turkey; 4Department of Orthopedics, Ac&inodot;badem Mehmet Ali Ayd&inodot;nlar University School of Medicine, &Idot;stanbul, Turkey; 5Department of Pathology, Ac&inodot;badem Mehmet Ali Ayd&inodot;nlar University School of Medicine, &Idot;stanbul, Turkey; 6Department of Radiology, Ac&inodot;badem Mehmet Ali Ayd&inodot;nlar University School of Medicine, &Idot;stanbul, TurkeyCorrespondence: Emel Öztürk Durmaz, Ac&inodot;badem Maslak Hospital, Büyükdere Caddesi 40, Maslak, Istanbul, 34457, Turkey, Tel +90 (212) 304 46 19, Fax +90 (212) 286 15 66, Email emelerkek@yahoo.comAbstract: CLOVES syndrome is a novel sporadic mosaic segmental overgrowth syndrome, currently categorized under the canopy of PROS (PIK3CA-related overgrowth spectrum) disorders. All PROS disorders harbor heterozygous postzygotic activating somatic mutations involving the PIK3CA gene. As an upstream regulator of the PI3K/AKT/mTOR signal transduction pathway, activating mutations of PIK3CA gene commence in uncontrolled growth of cutaneous, vascular (capillaries, veins, and lymphatics), adipose, neural, and musculoskeletal tissues. The excessive growth is segmental, patchy, asymmetric, and confined to body parts affected by the mutation. The term ‘CLOVES’ is an acronym denoting congenital lipomatous overgrowth, vascular malformations, epidermal nevi and spinal (scoliosis) and/ or skeletal anomalies. The syndrome is characterized by an admixture of overgrown tissues, derived mainly from mesoderm and neuroectoderm. Among PROS disorders, CLOVES syndrome represents the extreme end of the spectrum with massive affection of almost the entire body. The syndrome might judiciously be treated with medications hampering with the PI3K/AKT/mTOR signal transduction pathway. This article aims at reviewing the cutaneous and musculoskeletal manifestations of CLOVES syndrome, as the paradigm for PROS disorders. CLOVES syndrome and other PROS disorders are still misdiagnosed, underdiagnosed, underreported, and undertreated by the dermatology community.Keywords: CLOVES syndrome, PIK3CA-related overgrowth spectrum, cutaneous manifestations, port wine stains, lymphangiomas, lipomas, epidermal nevi

The underlying mechanisms of aggressive pituitary neuroendocrine tumors (pitNETs) are still unclear. The p16 protein, encoded by the CDKN2A tumor suppressor gene on chromosome 9p21, is commonly reported to be lost in numerous types of cancer. For this reason, this study examined to examine the status of homozygous deletion of CDKN2A in high-risk pitNETs. Thirty-eight high-risk pitNETs (30 male, 8 female) were analyzed for CDKN2A deletion by fluorescent in situ hybridization (FISH). Demographic characteristics such as sex, patient age at operation, and sellar magnetic resonance imaging findings including tumor size and invasion status were recorded. The frequency of CDKN2A homozygous deletion by FISH was 3/38 (7.89%) in the high-risk pitNET group. All of these three cases with CDKN2A homozygous deletion were invasive densely granulated lactotroph tumors (p = 0.000). CDKN2A deletion was not correlated with patient age, sex, cavernous sinus invasion (CSI), and tumor size (p > 0.05). The Ki-67 proliferation index was significantly correlated with CDKN2A homozygous deletion (p = 0.003). The mean Ki-67 proliferation index was 10.7% in pitNETs with CDKN2A homozygous deletion and the Ki-67 proliferation index in the whole study group was 4.1%. CSI was significantly correlated with the morphofunctional tumor types including lactotroph tumor, invasive null cell tumor, and invasive gonadotroph tumor (p = 0.021). These findings suggest a close correlation between inactivation of p16 gene and invasive lactotroph tumors. Further investigations are needed to expand on the mechanism of p16 (CDKN2A) gene deletion in high-risk pitNETs.

Pure tubular carcinoma (PTC) is a rare and well-differentiated tumor of the breast with high survival and low local recurrence rate. Sentinel lymph node biopsy (SLNB) is routinely used but still bears 5% risk of lymphedema. This study aims to investigate axillary involvement rate and necessity of axillary staging in clinically early PTCs. Thirty-seven PTCs in 36 patients between 2010 and 2017 were evaluated retrospectively. Histopathological features, sentinel lymph node detection rate, axillary involvement, and adjuvant treatments were recorded. Median pathological tumor size was 8 (3–18) mm. Median follow-up was 58 (21–106) months. Three patients had multi-focal and one patient had multi-centric tumor. While none of the tumors exhibited lymphovascular invasion, all tumors presented ER+ and Her-2 negative. Thirty-three tumors presented PR+. Median Ki-67 was 6% (1–16%). Histologic grade was low except one patient, whereas nuclear grade was low in 12 (32%) patients and intermediate in 25 (68%) patients. SLNB was positive in two patients in whom both were micro-metastases. Thirteen tumors (35%) were found to have a tumor size of ≥ 10 mm, whereas 24 (65%) tumors were found to be

The number of breast cancer cases and mortality rate has been on the rise globally. For effective treatment and curbing the mortality rate, early diagnosis is paramount. To evaluate the effectiveness of treatment, a fundamental step is histopathological examination of the state of nuclei. However this is a challenging task for various reasons. Accordingly, we perform nuclei detection in breast cancer histopathology images using RetinaNet with a ResNet-152 as the feature extractor. The data used for training and validation of the model was carefully collected at our partner teaching hospital. A mean Average Precision (mAP) of 78% was achieved by optimizing the Focal Loss. Thus outperforming current state-of-the-art methods which have been reported in the literature.

Despite the high prevalence of lung cancer among other primary tumors, metastasis of this particular malignancy in the breast is very rare. We report three new cases of lung cancer with breast metastases and discuss radiological and clinical findings. Radiologically, each case displayed different characteristics. First, one of them had bilateral superficially and deeply located irregular lesions. Second, the patient presented with findings similar to inflammatory breast cancer. The third case had a circumscribed mass, resembling a benign complicated cyst. To guide clinicians for proper patient management, radiologists should be aware of the scope of typical and atypical imaging findings of metastatic involvement of the breast.

Colorectal cancer; FFPE clinical tissue samples; Microsatellite instability Cancer colorrectal; Muestras de tejido clínico FFPE; Inestabilidad de microsatélites Càncer colorectal; Mostres de teixit clínic FFPE; Inestabilitat del microsatèl·lits Microsatellite instability (MSI) is present in 15–20% of primary colorectal cancers. MSI status is assessed to detect Lynch syndrome, guide adjuvant chemotherapy, determine prognosis, and use as a companion test for checkpoint blockade inhibitors. Traditionally, MSI status is determined by immunohistochemistry or molecular methods. The Idylla™ MSI Assay is a fully automated molecular method (including automated result interpretation), using seven novel MSI biomarkers (ACVR2A, BTBD7, DIDO1, MRE11, RYR3, SEC31A, SULF2) and not requiring matched normal tissue. In this real-world global study, 44 clinical centers performed Idylla™ testing on a total of 1301 archived colorectal cancer formalin-fixed, paraffin-embedded (FFPE) tissue sections and compared Idylla™ results against available results from routine diagnostic testing in those sites. MSI mutations detected with the Idylla™ MSI Assay were equally distributed over the seven biomarkers, and 84.48% of the MSI-high samples had ≥ 5 mutated biomarkers, while 98.25% of the microsatellite-stable samples had zero mutated biomarkers. The concordance level between the Idylla™ MSI Assay and immunohistochemistry was 96.39% (988/1025); 17/37 discordant samples were found to be concordant when a third method was used. Compared with routine molecular methods, the concordance level was 98.01% (789/805); third-method analysis found concordance for 8/16 discordant samples. The failure rate of the Idylla™ MSI Assay (0.23%; 3/1301) was lower than that of referenced immunohistochemistry (4.37%; 47/1075) or molecular assays (0.86%; 7/812). In conclusion, lower failure rates and high concordance levels were found between the Idylla™ MSI Assay and routine tests.

In an effort to ease the job of pathologists while examining Hematoxylin and Eosin stained breast tissue, this study presents a deep learning-based classifier of nuclear pleomorphism according to the Nottingham grading scale. We show that high classification accuracy is attainable without pre-segmenting the cell nuclei. The data used in the experiments was acquired from our partner teaching hospital. It consists of image patches that were extracted from whole slide images. Using the labeled data, we compared the performance of three state-of-the-art convolutional neural networks and tested the trained model on the unseen testing data. Our experiments revealed that the densely connected architecture (DenseNet) outperforms the residual network (ResNet) and the dual path networks (DPN) in terms of accuracy and F1 score. Specifically, we reached an overall validation accuracy and F1 score of over 0.96 and 0.94 respectively.

Amaç: Bu çalışmanın amacı erkek kano sporcularının müsabaka öncesi ve sonrası bazı fiziksel ve fizyolojiközellikleri ile akciğer fonksiyon kapasitelerini belirlemektir..Materyal ve Metod: Çalışmaya Rize-Ardeşen’de düzenlenen Türkiye Kano Şampiyonasına katılan 18 erkeksporcu gönüllü olarak katıldı. Boy, kilo, kalp atım sayısı, sistolik ve diastolik kan basıncı değerleri ve solunumfonksiyonlarını belirlemek için bazı testler yapıldı. Elde edilen verilerin değerlendirilmesinde SPSS 20 paketprogramında tanımlayıcı istatistik ve eşleştirilmiş T testi yapıldı.Bulgular: Kano sporcularının yaş ortalamaları 17,5±1,72 boy ortalamaları 1,73±,06m kilo ortalamaları65,22±8,46kg ve beden kitle indeksi ortalamaları 21,74±2,37kg/m2 olarak tespit edildi. Kano sporcularınınKalp atım sayıları incelendiğinde müsabaka öncesi 104,38±11,92, müsabaka sonrası 125,72±19,81 olaraktespit edildi. Kan basıncı değerleri incelendiğinde, sistolik kan basıncı değerleri müsabaka öncesi 11,61±1,33,müsabaka sonrası 13,11±1,49, diastolik kan basıncı değerleri müsabaka öncesi 6,66±1,28, müsabaka sonrası6,88±1,23 olarak tespit edildi. Solunum parametreleri incelendiğinde, zorlu vital kapasite (FVC) müsabakaöncesi 3,68±1,13 cm, müsabaka sonrası 3,28±1,1 cm, 1. saniye zorlu ekspiratuar volüm (FEV1) müsabakaöncesi 3,63±,81 cm, müsabaka sonrası 3,2±92 cm, zirve ekspiratuar akım (PEF) müsabaka öncesi 7,71±2,69cm, müsabaka sonrası 7,64±2,48 cm, olduğu tespit edildi. Sonuç olarak kalp atım sayıları ve sistolik kanbasıncı değerlerinde artış ve istatiksel olarak anlamlı farklılık tespit edildi (pAnahtar Kelimeler: kalp atım sayısı, kan basıncı, kano, solunum fonksiyonları&nbsp

The SARS-CoV-2 virus caused the most severe pandemic around the world, and vaccine development for urgent use became a crucial issue. Inactivated virus formulated vaccines such as Hepatitis A, oral polio vaccine, and smallpox proved to be reliable approaches for immunization for prolonged periods. During the pandemic, we produced an inactivated SARS-CoV-2 vaccine candidate, having the advantages of being manufactured rapidly and tested easily in comparison with recombinant vaccines. In this study, an inactivated virus vaccine that includes a gamma irradiation process for the inactivation as an alternative to classical chemical inactivation methods so that there is no extra purification required has been optimized. The vaccine candidate (OZG-38.61.3) was then applied in mice by employing the intradermal route, which decreased the requirement of a higher concentration of inactivated virus for proper immunization, unlike most of the classical inactivated vaccine treatments. Hence, the novelty of our vaccine candidate (OZG-38.61.3) is that it is a non-adjuvant added, gamma-irradiated, and intradermally applied inactive viral vaccine. Efficiency and safety dose (either 1013 or 1014 viral copy per dose) of OZG-38.61.3 was initially determined in Balb/c mice. This was followed by testing the immunogenicity and protective efficacy of OZG-38.61.3. Human ACE2-encoding transgenic mice were immunized and then infected with a dose of infective SARS-CoV-2 virus for the challenge test. Findings of this study show that vaccinated mice have lower SARS-CoV-2 viral copy number in oropharyngeal specimens along with humoral and cellular immune responses against the SARS-CoV-2, including the neutralizing antibodies similar to those shown in Balb/c mice without substantial toxicity. Subsequently, plans are being made for the commencement of Phase 1 clinical trial of the OZG-38.61.3 vaccine for the COVID-19 pandemic.

Breast cancer, being the second most frequently seen cancer globally, is the most common cancer among women. Early and accurate diagnosis is dependent on the correct identification of nuclei in histopathological images, which is a very tedious task when it is done manually. The proposed method is a deep learning model using U-Net architecture supplied with various pre- and post-processing techniques. The model was trained and tested on a unique dataset. Our model performed the nuclei segmentation task with a Dice score of 0.84, a true negative rate (TNR) of 0.95, a true positive rate (TPR) of 0.84, and an accuracy rate of 0.93. To enhance the performance of our model, our planned future work includes increasing the number of histopathological images in our dataset.

Background:Morton’s neuroma (MN) is mechanical neuropathy of plantar interdigital nerve. It is one of the most common causes of forefoot pain. One of the most undesirable complications of MN surgery is recurrent neuroma. Excision level of MN is important to prevent recurrence. In this study, we aimed to find the relation resection lenght of MN to clinical results of MN surgery cases. Methods:76 samples sent with the diagnosis of Morton neuroma to the pathology department of our hospital between years 2010-2019. 66 patients whose clinical results were available were included in the study. Mean age was 41,5 (between 21 to 70). All of 66 patients were primary diagnosed 22 of them was left foot and the other 170 were right foot. 50 of them were female, and 16 were male. Recurrent neuromas, pathological sample more than one piece from one surgical site were excluded from the study. 72 of them were evaluated as a clinically and compare the sample lenght.Results:76 pathological specimens were prepared and examined by the same pathologist. Gross pathological appearance and histopathology findings were recorded. Mean sample length was 2,05 cm (between 0,7cm and 3,5 cm). 68 samples was smaller (89.5%) than 3 cm and only 8 sample (10.5%) was bigger than 3 cm. Average interdigital neuroma score improved from 20 to 62 points following the surgery (p

Introduction: Morton’s neuroma (MN) is mechanical neuropathy of plantar interdigital nerve. It is one of the most common causes of forefoot pain. One of the most undesirable complications of MN surgery is recurrent neuroma. Excision level of MN is important to prevent recurrence. In this study, we aimed to figure out preferred excision levels of orthopedic surgeons by evaluating pathological samples. Methods: 192 samples sent with the diagnosis of Morton neuroma to the pathology department of our hospital between years 2010-2017 were added to our study. Mean age was 45,8 (between 23 to 73). All of 192 patients were primary diagnosed 22 of them was left foot and the other 170 were right foot was. 139 of them were female, and 53 were male. Recurrent neuromas, pathological sample more than one piece from one surgical site were excluded from the study. Results: 192 pathological specimens were prepared and examined by the same pathologist. Gross pathological appearance and histopathology findings were recorded. Mean sample length was 2,05 cm (between 0,8cm and 6 cm).145 samples was smaller (75.5%) than 3cm and only 47 sample (24.5%) was bigger than 3 cm.Conclusion: In conclusion our database results showed that majority of surgeons didn't take into account plantarly directed nerve branches.

Aim:Multifocal papillary thyroid cancer (MPTC) has aggressive and poor prognosis. The main aim of this study was to evaluate the lymph node metastasis pattern in MPTC patients.Methods:We retrospectively investigated the records of 2530 patients who underwent thyroidectomy for papillary thyroid cancer between January 2010 and December 2017. The age, gender, tumor size, thyroid capsule invasion and neck metastatic disease were evaluated in 515 of these patients having MPTC.Results:We compared multifocal and unifocal papillary thyroid cancer patients considering papillary thyroid capsule invasion (29.9%/10.86%), mean tumor diameter (15.9 mm/16.1 mm), central lymph node metastasis (56.5%/18.3%) and lateral neck lymph node metastasis (23.1%/6.3%). Capsule invasion was associated with an increased risk of multifocal disease. The incidence of capsular invasion and central and lateral neck metastases in MPTC patients was statistically significantly higher than in patients with unifocal thyroid papillary cancer (p

Lipomatous tumors accompanied by spindle cell component are not frequently encountered, and there are still problems regarding their differential diagnosis, nature, and nomenclature. To contribute to ongoing efforts, we present the clinical, histologic, and immunohistochemical characteristics of 20 cases of spindle cell lipomatous tumors with atypical features that may also be called atypical spindle cell/pleomorphic lipomatous tumors. Of the patients, 13 were men and 7 were women with an average age of 57.5 years. The most commonly affected site was the extremities. Twelve tumors arose in the subcutaneous tissue, while eight cases were located in the deep soft tissues. Tumor margins were often ill-defined with invasion into the surrounding tissues. Microscopic examination revealed a wide spectrum of histologic features. All cases consisted of poorly marginated proliferation of mildly atypical spindle cells set in a fibrous or myxoid stroma with a variable amount of adipocytic component showing variation in adipocyte size and scattered nuclear atypia and frequent univacuolated or multivacuolated lipoblasts. Tumor cellularity and the relative proportion of the components were highly variable. One tumor showed morphologic features evocative of dedifferentiation and another one exhibited histological features resembling pleomorphic liposarcoma. None of the patients had recurrence or metastasis at follow-up.

Graphical abstract, Highlights • IQGAP proteins demonstrated differential expression between CV-PTC and FV-PTC. • Proteome similarities between benign and FV-PTC hampered accurate unsupervised clustering. • Changes in actin cytoskeleton proteins play predominant roles in thyroid pathology., Introduction Fine Needle Aspiration Biopsy (FNAB) allows the cytological differentiation of benign and malignant thyroid nodules. However, the method itself is not adequate in determining some cases. For example, the diagnosis of Follicular Variant Papillary Thyroid Carcinoma (FV-PTC) can be challenging. In the current study we investigate the protein profiles of FV-PTC and classical variant PTC (CV-PTC) with no lymph node metastasis and compare it with benign thyroid tissue. Method We used CV-PTC (n = 6), FV-PTC (n = 6) and benign thyroid tissues (n = 6) to prepare tissue lysates. Proteins from each group were trypsin and lys-C digested. The samples were analyzed on a Q Exactive Orbitrap mass spectrometer. Results We identified 2560 proteins across all 18 specimens. Protein profiles revealed that there was no clear distinction between benign and FV-PTC samples. However, further examination of our data showed that proteins in energy metabolism have altered in FV-PTC. Proteomic pathway analysis showed marked alteration of the actin cytoskeleton proteins, especially several members of Arp2/3 complex were significantly increased in CV-PTC. We made the novel observation that IQGAP1 protein was significantly increased in CV-PTC, whereas IQGAP2 protein was highly expressed in FV-PTC lesions, suggesting differential roles of IQGAP proteins in thyroid pathology. Conclusion In the present study, mass spectrometry based label free quantification approach was applied to investigate the protein profiles of FV-PTC, CV-PTC and benign thyroid tissues. This study pointed out that actin cytoskeleton proteins, IQGAP proteins and changes in energy metabolism play predominant roles in thyroid pathology.

Non-small cell lung cancer (NSCLC) is a frequent tumor entity with high mortality. Although several newly discovered chromosomal translocations and mutations opened new horizons for targeted therapy, literature still lacks large series of NSCLC with chromosomal abberations and their correlations with histological and clinical features. We present a case of echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) translocation positive adenocarcinoma of the lung with an unusual metastatic pattern in a 29-year-old young woman. Conclusion: Young adult non-smoker female patients with an unexplained pleural effusion and signs of metastatic disease should alert the physicians straight away for all types of malignancies including lung cancer. Any skin lesions should be evaluated carefully, biopsies should be done to exclude metastasis in urgency. On the other hand, an uncommon clinical presentation of a lung cancer requires corresponding molecular testing rapidly in order to offer the best treatment option. (C) 2017 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license.

Relapsed and refractory CD19-positive B-cell acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL) are the focus of studies on hematological cancers. Treatment of these malignancies has undergone recent transformation with the development of new gene therapy and molecular biology techniques, which are safer and well-tolerated therapeutic approaches. The CD19 antigen is the most studied therapeutic target in these hematological cancers. This study reports the results of clinical-grade production, quality control, and in vivo efficacy processes of ISIKOK-19 cells as the first academic clinical trial of CAR-T cells targeting CD19-expressing B cells in relapsed/refractory ALL and NHL patients in Turkey.We used a lentiviral vector encoding the CD19 antigen-specific antibody head (FMC63) conjugated with the CD8-CD28-CD3ζ sequence as a chimeric antigen receptor (CAR) along with a truncated form of EGFR (EGFRt) on human T-lymphocytes (CAR-T). We preclinically assessed the efficacy and safety of the manufactured CAR-T cells, namely ISIKOK-19, from both healthy donors’ and ALL/NHL patients’ peripheral blood mononuclear cells.We showed significant enhancement of CAR lentivirus transduction efficacy in T-cells using BX-795, an inhibitor of the signaling molecule TBK1/IKKƐ, in order to cut the cost of CAR-T cell production. In addition, ISIKOK-19 cells demonstrated a significantly high level of cytotoxicity specifically against a CD19+ B-lymphocyte cancer model, RAJI cells, in NOD/SCID mice.This is the first report of preclinical assessment of efficacy and safety analysis of CAR-T cells (ISIKOK-19) targeting CD19-expressing B cells in relapsed/refractory ALL and NHL patients in Turkey.Relaps/refrakter CD19-pozitif B-hücreli akut lenfoblastik lösemi (ALL) ve Hodgkin dışı lenfoma (NHL), hematolojik kanserlerle ilgili çalışmaların odak noktasıdır. Bu malignitelerin tedavisi, daha güvenilir ve iyi tolere edilen terapötik yaklaşımlar olan, yeni gen terapisi ve moleküler biyoloji tekniklerinin geliştirilmesi ile son zamanlarda dönüşüm geçirmiştir. CD19 antijeni, bu hematolojik kanserlerde en çok çalışılan terapötik hedeftir. Bu çalışma, Türkiye’de relaps/refrakter ALL ve NHL hastalarında, ilk akademik klinik deneme için kullanılması amacıyla, CD19 eksprese eden B hücrelerini hedefleyen CAR-T (ISIKOK-19) hücrelerinin klinik sınıf üretimi, kalite kontrolü ve in vivo etkinlik süreçlerinin sonuçlarını bildirmektedir.Bu çalışmada, insan T-lenfositleri (CAR-T) üzerinde kesilmiş EGFR (EGFRt) formu ile birlikte kimerik bir antijen reseptörü (CAR) olarak CD8-CD28-CD3ζ sekansı ile konjuge CD19 antijene özgü antikor başını (FMC63) eksprese eden bir lentiviral vektör kullandık. Hem sağlıklı donörlerin hem de ALL/NHL hastalarının periferal kan mononükleer hücrelerinden üretilen CAR-T (ISIKOK-19) hücrelerinin etkinliğini ve güvenliğini klinik öncesi olarak değerlendirdik.CAR-T hücre üretiminin maliyetini düşürmek için sinyal molekülü TBK1/IKKƐ’nın bir inhibitörü olan BX-795 kullanarak T-hücrelerinde CAR lentivirüs transdüksiyon etkinliğinin önemli ölçüde arttığını gösterdik. Ek olarak, ISIKOK-19 CAR-T hücrelerinin, NOD/SCID farelerinde özellikle bir CD19 + Blenfosit kanser modeli olan RAJI hücrelerine karşı önemli ölçüde ve yüksek seviyede sitotoksisite gösterdiğini değerlendirdik.Bu çalışma, Türkiye’de relaps/refrakter ALL ve NHL hastalarında CD19 eksprese eden B-hücrelerini hedefleyen CAR-T hücrelerinin ilk akademik klinik çalışması olarak ISIKOK-19 hücrelerinin klinik sınıf üretimi, kalite kontrolü ve in vivo etkinlik süreçlerinin sonuçlarını bildirmektedir.

ABS TRACT Malignant schwannoma is rarely found in the paranasal sinuses and nasal cavity. Only 21 cases have been reported in the literature so far. Only four of the 21 cases were reported to be primarily originated from the maxillary sinus. In this article, a 44-year-old woman with a right maxillary sinus malignant schwannoma is presented. Right partial maxillectomy with lateral rhinotomy approach followed by a postoperative course of radiotherapy and chemotherapy was performed as the treatment. This mass was confirmed as a malignant schwannoma in histological examination and immunohistochemical staining. There was no tumor recurrence or distant metastases for 22 months after the treatment. She died from brain metastasis and sepsis 37 months after the operation.

Telomeres, and telomere length in particular, have broad significance for genome biology and thus are prime research targets for complex diseases such as cancers. In this context, BRCA1 and BRCA2 gene mutations have been implicated in relationship to telomere length, and breast cancer susceptibility. Yet, the linkages among human genetic variation and telomere length in persons with high hereditary cancer risk are inadequately mapped. We report here original findings in 113 unrelated women at high hereditary risk for breast cancer, who were characterized for the BRCA1 and BRCA2 mutations using next-generation sequencing. Thirty-one BRCA2 and 21 BRCA1 mutations were identified in 47 subjects (41.6%). The women with a mutation in BRCA1 and/or BRCA2 genes had, on average, 12% shorter telomere compared to women with no BRCA1 or BRCA2 mutation ( p = 0.0139). Moreover, the association between telomere length and BRCA mutation status held up upon stratified analysis in those with or without a breast cancer diagnosis. We also indentified two rare mutations, c.536_537insT and c.10078A>G, and a novel mutation c.8680C>G in BRCA2 that was studied further by homology modeling of the DNA binding tower domain of BRCA2 and the structure of the protein. These data collectively lend evidence to the idea that BRCA1 and BRCA2 mutations play a role in telomere length in women at high hereditary risk for breast cancer. Further clinical and diagnostics discovery research on BRCA1 and BRCA2 variation, telomere length, and breast cancer mechanistic linkages are called for in larger study samples.

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Objectives: Programmed cell death ligand 1 (PD-L1) is the most important immune checkpoint protein in immune defense against tumors. PD-1/PD-L1 inhibitors are considered an option in cancer treatments. The evaluation of PD-L1 immunohistochemical staining is used as a biomarker to determine the decision and response of the use ofthese inhibitory drugs. There is a wide variety of clones and platforms for the PD-L1 antibody, and each pathology department uses different clones and platforms which causes confusion. Therefore, in this study, we evaluated the immunohistochemical staining of different clones in the same tumor. Methods: Overall, 90 cases comprising 47 lung, 11 breast, 9 colon, 6 stomach, and 7 pancreatic carcinomas and 10 other tumors were included in the study. Of these, 43 specimens were obtained by resection, 40 by tru-cut biopsy, and 7 by endoscopic biopsy. Sections prepared from formalin-fixed paraffin-embedded blocks were evaluated immunohistochemically with SP142 and SP263 clones. Results: In this study, we observed positive staining in 48.8\% (n=44) and negative staining in 51.2\% (n=46) among all cancers with SP263 clone, and positive staining in 33.3\% (n=30) and negative staining in 66.7\% with SP142 clone as well. This study also showed that compared to SP263, SP142 clone stained tumor cells less in lung, colon, stomach, pancreatic, and other carcinomas. Conclusion: In this study, we found different staining percentages for SP263 and SP142 in the same tumor. Pathologists conducting immunohistochemical studies for PD-L1 should indicate the staining percentages of tumors and the antibody clone they used in the reports. Meanwhile, oncologists should keep in mind which clone was stained, and that selecting SP142 is less positive to correct patients who can receive appropriate immunotherapy.

A laryngeal leiomyosarcoma is a very rare tumor that originates from heterotopic mesenchymal tissues or smooth muscle cells. It is diagnosed by immunohistochemical staining.

Purpose Metaplastic breast carcinoma (MBC) is a rare aggressive type of breast cancer, which accounts for less than 1% of breast tumors. Since its recognition as a distinct pathological entity in 2000, number of MBC patients has been increasing over years. We aimed to report a series of 7 cases of MBC treated in our clinics. Materials and methods Between 2006 and 2015, 7 cases with diagnosis of MBC were retrospectively reviewed. Patients' characteristics, clinicopathological features and types of surgery were evaluated. Results All patients were female with a median age of 51(40–65) years. Median tumor size was 40 mm (35–85 mm). Two patients had breast-conserving surgery and 4 patients had mastectomy. One patient received chemotherapy due to extensive metastatic disease at the time of presentation. Only one patient had one positive sentinel lymph node with no other involvement in the non-sentinel nodes. Two patients had spindle cell carcinoma, 2 patients had pure epithelial type, and 3 patients had mixed epithelial and mesenchymal type MBC. Most common component of MBC was squamous cell metaplasia that was found in 4 out of 7 patients. Six patients had triple negative tumors except the patient with disseminated disease. This patient had estrogen receptor positive, progesterone receptor negative tumor with human epithelial receptor-2 (HER2) over-expression. Median Ki67 score measured in 5 patients was 57% (40–95%). Conclusion Our small series is consistent with the literature. MBC rarely metastasize to axillary lymph nodes despite large size and are usually triple negative with high Ki-67 scores indicating aggressiveness and lack of response to hormonal therapy. Larger series of patients are needed to find and test new biomarkers to develop potential targeted therapy for subgroups of the disease.

Background: Carpal tunnel syndrome(CTS) is the most frequent compressive neuropathy of upper extremity .Median nerve is compressed under flexor retinaculum because of primary or secondary reasons. Although primary CTS may have different causes, idiopathic CTS's ethiology is unclear We aimed to evaluate tenosynovial tissue change under flexor retinaculum as a cause of idiopathic CTS even more as a possible cause of recurrent CTS. Materials and Methods: We operated 175 patients with carpal tunnel syndrome who had median nerve compression. 110 patients were diagnosed as idiopathic CTS were included at our study. Open carpal tunnel release was performed by same surgeon and synovial samples were taken from synovial connective tissue under median nerve for pathological examination. Results: All patients were followed-up 22 months ( 12 to 35 months ) prospectively. Mean age was 45 years( 22 to 65). Preop VAS score was 6 post op VAS score was 1. Synovial hypertrophy was detected at 38 of 110 patients(34%). Other pathological results were; 13 reactive synovitis (11%), 8 ganglion(7.2%) , 51 fibrohyaline nodulation(46.3%). Conclusions: We recommend the evalution of tenosynovial tissue under flexor retinaculum after releasing the retinaculum. If there is an inflammation or a hypertrofi or a mass effect, surgeon must do partial tenosynovectomy to decrease the volume of the carpal tunnel and to prevent recurrence.

Introduction: The lack of papillary structures and faint and/or unclear core features of follicular variant of papillary thyroid carcinoma (FV-PTC) may hamper the definitive fine needle aspiration biopsy -based diagnosis. Recently, the nomenclature of noninvasive encapsulated FV-PTC was revised to "noninvasive follicular thyroid neoplasms with papillary-like nuclear features" (NIFTP). However, it remains inconclusive whether or not the peptide patterns differ between NIFTP and encapsulated FV-PTC. The main objectives of this study were to investigate the viability of matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) in the pathological assessment of NIFTP and to evaluate the discriminatory power of MALDI MSI for the classification of classical variant of PTC (CV-PTC), NIFTP, and encapsulated FV-PTC. Methods: MALDI MSI was employed to investigate the changes in peptide profiles from 21 formalin-fixed paraffin-embedded (FFPE) tissue samples (n = 7 from each group of CV-PTC, NIFTP, and FV-PTC). Six out of seven FV-PTC FFPE tissue samples were encapsulated FV-PTC; only one was infiltrative FV-PTC. Liquid chromatography-tandem mass spectrometry was used for the identification of the peptide signals detected in MALDI MSI. Results: Using receiver operating characteristics analysis, 10 peptide signals distinguished NIFTP from normal thyroid parenchyma (area under the curve [AUC] >0.80). To evaluate the discriminatory power of MALDI MSI, statistically significant peptide signals (n = 88) within three groups were used for hierarchical clustering. The method had high discriminatory power for distinguishing CV-PTC from NIFTP and FV-PTC (encapsulated and infiltrative). The majority of the NIFTP and encapsulated FV-PTC were clustered together, indicating that NIFTP could not be distinguished from encapsulated FV-PTC. However, infiltrative FV-PTC FFPE tissue samples had the furthest distance from all the NIFTP cases. High signal intensities of S100-A6, vimentin, and cytoplasmic actin 1 were detected in FV-PTC, prelamin A/C in CV-PTC, and 60S ribosomal protein L6 and L8 in NIFTP tissues. Conclusions: MALDI MSI, a powerful tool combining histological and mass spectrometric data, enabled the differentiation of NIFTP from normal thyroid parenchyma. Although NIFTP is a recent definition that replaces noninvasive encapsulated FV-PTC, the peptide profiles of NIFTP and encapsulated FV-PTC were found to be similar.

To investigate the effect of azoospermia type on fertilization and clinical pregnancy rates when microdissection testicular sperm extraction (TESE) is performed for sperm retrieval in nonobstructive azoospermia (NOA).STUDY DESIGN: Patients who underwent microdissection TESE for NOA and conventional TESE for obstructive azoospermia (OA) were included in the study. Intracytoplasmic sperm injection (ICSI) results were compared between groups.The mean ages in the 2 groups were similar. FSH and LH levels in the NOA group were significantly higher than those of the OA group. Between groups there was no statistically significant difference in testosterone levels. The sperm retrieval rate was 58.56% in NOA. Fertilization and clinical pregnancy rates were similar for patients with NOA and OA.In patients with NOA, microdissection TESE accurately determines active spermatogenesis areas via the high identification power of the operative microscope. From these areas surgeons can collect healthier spermatozoa, which can result in better ICSI outcomes, the results of which are similar to those with OA.