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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.

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.

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.

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]

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

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.

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.

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.

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.

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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.

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

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.

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.

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: Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare vascular proliferative disorder mainly located in the periauricular region. The etiopathogenesis of ALHE is unknown, and it is still controversial as to whether the entity represents a benign vascular neoplasm or an inflammatory process. Aim: Recently, the intracytoplasmic staining pattern of Wilms tumor 1 (WT1) on immunohistochemistry has highlighted true vascular neoplasms, such as microvenular hemangioma, tufted angioma, and spindle cell hemangioma, which has made it helpful to distinguish ALHE from vascular malformations, as there is a negative staining pattern in the other entities. We aimed to investigate the immunoreactivity of ALHE specimens for WT1 as well as glucose transporter protein 1 (GLUT1) immunohistochemistry, an important and sensitive marker for the diagnosis of infantile hemangioma, which recently has been described to label other hemangiomas, such as verrucous hemangioma. Material and methods: Clinical data and histopathological specimens from patients diagnosed with ALHE were reviewed, and immunohistochemical staining and microscopic analysis for WT-1 and GLUT1 were performed. Results: Intracytoplasmic endothelial staining of WT1 was detected in 19 of 20 ALHE specimens. GLUT1 was not detected in any ALHE specimen. Conclusions: We conclude that ALHE may represent a true hemangioma (i.e., benign vascular neoplasia) characterized by an eosinophil- and lymphocyte-rich inflammatory component as opposed to the reactive inflammatory dermatosis with a positive intracytoplasmic staining pattern for WT1. As far as we are aware, WT1 staining for ALHE has not been described to date.

BACKGROUND: Differentiation of psoriasis from non-psoriasis psoriasiform dermatitis (NPPD) may be difficult for dermatopathologists, as lack of distinctive histopathological features in a subset of cases may cause confusion in diagnosis. OBJECTIVE: As the prototype of psoriasiform dermatitis, psoriasis is a hyperproliferative skin disorder with increased epidermal turnover compared with NPPD, we investigated the role of proliferation markers, Ki-67 and Cyclin D1 as diagnostic tools to differentiate psoriasis from other psoriasiform dermatitis. METHODS: Histopathological specimens of psoriasis (n = 35) and NPPD (n = 36, 14 pityriasis rubra pilaris, 12 pityriasis rosea and 10 lichen simplex) cases were reviewed and immunohistochemically stained for Ki-67 and Cyclin D1. Ki-67 and Cyclin D1 positive cells were counted for suprabasal, and total epidermal immunostaining per mm(2). RESULTS: Suprabasal and total epidermal cell counts for Ki-67 were found to be significantly higher in the psoriasis group compared with the NPPD group (p < 0.05). An important and interesting feature was the presence of a cut-off value for the suprabasal/total epidermal cell count ratio of 75% for Ki-67 immunostaining, which was higher in all patients having psoriasis (range, 77.1% - 92.4%) and lower in all NPPD cases (range, 21.0% - 73.3%). However, suprabasal Cyclin D1 cell counts were higher in the psoriasis group compared with the NPPD group (p < 0.05), total epidermal Cyclin D1 cell counts were not statistically significant in either group (p = 0.167), and a cut-off value for suprabasal/total epidermal cell count ratio to distinguish these two entities was not detected using this immunostain. CONCLUSIONS: We suggest that Ki-67 is a more sensitive marker than Cyclin D1 in terms of having a cutoff value of 75% for the suprabasal/total epidermal immunoreactive cell count ratio, which we believe could be useful for dermatopathologists in differentiating psoriasis from other psoriasiform dermatitis.

Thrombocytopenia is a frequent finding in patients with solid tumors. It is usually caused by bone marrow infiltration or by myelosuppression due to anticancer therapy; however immune thrombocytopenia (ITP) associated with solid tumors is rare. Neuroblastoma is the most common extracranial solid tumor in children. Here we report the case of a two-year-nine-month-old patient with adrenal neuroblastoma who presented with ITP. Paraneoplastic ITP was considered in the differential diagnosis. Bone marrow infiltration and other causes of thrombocytopenia were excluded and the patient was treated with intravenous immunoglobulin and tumor resection. Platelet count increased rapidly after surgery and complete remission of ITP was achieved.

Appendiceal neuroendocrine tumor (NET) is usually an incidental finding after a laparotomy for appendectomy, with a frequency of 2–5 cases per 1,000 appendectomies. Most appendiceal NETs are less than 2 cm in size and nonmetastasizing [1]. We report an unusual case of an appendiceal NET coexisting with severe endometriosis. The NET did not show any changes on the appendiceal surface and was palpated via laparoscopic graspers. It was small and of low histological grade; however, it showed, in contrast to previous reports, local and multiple regional lymph node metastases. Based on a search between 1966 and 2012, we conclude that this co-existence is so far unique in the literature.

A 28-year-old woman presented in her first pregnancy was admitted with severe hyperemesis gravidarium. Increased nuchal translucency with cardiac anomaly and omphalocele at the first trimester was observed at the ultrasound examination. Chorionic villus biopsy confirmed triploidy. The combination of type I and type II triploidy patterns were seen together in the second trimester of the pregnancy. Although the symptoms due to increased human chorionic levels occured, at the pathologic investigation there were no molar changes in the placenta. Here we report a case of uncommon presentation of triploidy.

Kikuchi-Fujimoto disease (KFD) or histiocytic necrotizing lymphadenitis is an idiopathic, benign, self-limited, rare disease. This disease is mostly encountered in Asia and in young adult. Cervical lymph node involvement is the most common symptom. In addition, fever, fatigue, increase in erythrocyte sedimentation rate, and leukocytopenia may also occur. A specific diagnosis and treatment for this disease has not been defined. The diagnosis of this disease however can be diagnosed with excision of lymph node and histopathological examination. KFD can often resolve spontaneously. If there is no spontaneous regression, oral corticosteroid therapy can be applied. In this case report, we were referred a rare case of Kikuchi-Fujimoto disease, presented with the cervical lymphadenopathy, increased erythrocyte sedimentation rate, and fever.

Background Because of the poor sensitivity of urinary cytological findings for the diagnosis of especially low grade urinary bladder carcinoma, new molecular diagnostic methods have been proposed. We decided to verify the ImmunoCyt/uCyt+ (UCyt+™) test and cytology combination and cytokeratin 20 (CK20) and cytology combination in urine as possible diagnostic and monitoring tool for bladder cancer. Methods Evaluation of CK20 expression and UCyt+™ was performed in urine of 90 patients of which 54 with bladder cancer with primary/recurrent diagnosis (low grade urothelial carcinoma (LGUC) = 23/8 patients, high grade urothelial carcinoma (HGUC) = 18/5 patients), and 36 patients as control; except of neoplastic bladder disease patients. For the evaluation of the three tests, CK20 and UCyt+™ tests were combined with urine cytology and compared with each other. Results The overall sensitivity detected for each tumor marker was as follows: for urine cytology was 75.9% and UCyt+™ was 83.3%, for CK20 70.4%, while the specificity was 66.7% for urine cytology and 86.1% for UCyt+™ and 83.3% for CK20. The sensitivity of cytology and UCyt+™ combination was higher (88.9%) than the sensitivity cytology and CK20 combination (77.8%). The simultaneous use of the three markers, sensitivity was reaching 92.5%. Conclusion The UCyt+™ test and CK20 expression are valid tools for the performance of adjunctive analyses with conventional cytologic examination.