Search

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.

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.

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.

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.

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

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.

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.

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.

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.

Background In 2016, the Papanicolaou Society of Cytopathology (PSC) issued a new classification scheme for respiratory cytology. We aim to evaluate our samples according to this classification and to assess risk of malignancy and diagnostic yield of different cytological modalities. Methods Respiratory specimens (sputum, bronchial wash/brush, BAL and FNA) obtained between 2007 and 2016 were reclassified according to PSC guidelines. Risk of malignancy for each diagnostic category was determined. Diagnostic yield was evaluated based on three-categorical approach. Results One thousand, two hundred and ninety respiratory specimens were retrieved, of which 280 had histologic follow-up. Samples were reclassified as nondiagnostic 16%, negative for malignancy 53%, atypical 5.4%, neoplastic (benign neoplasm/low-grade carcinoma) 0.4%, suspicious for malignancy 2.1% and malignant 23.1%. Risk of malignancy for each category was 64.01% for ND, 48.27% for NM, 59.09% for A, 100% for N-B-LG; 90% for SM and 89.74% for M. When only malignant cases were considered positive tests, cytology sensitivity was 55% and specificity 88%. Conclusion Our results were in line with PSC guidelines, but the use of multiple cytological techniques may cause some discrepancies in overall diagnostic yield and in estimated risks of malignancy, which is important due to the widespread utilization of different cytological procedures.

Objective To define the accuracy and acceptability of ultrasonography-guided percutaneous needle core biopsy in diagnosis of renal masses. Methods The data of 42 consecutive patients on whom needle biopsies were performed and were surgically treated for suspicious renal masses in our clinic between January 2001 and April 2008 were evaluated. In all patients, needle biopsies were done percutaneously with an 18-gauge needle under local anesthesia in prone position with ultrasonography guidance. Two cores were taken from each tumor. The pathology results of biopsy and surgical specimens were compared. Results The mean age was 56.1 years (range, 21-77 years). The mean follow-up period was calculated as 44.8 months (range, 10-85 months). The abdominal computed tomography imaging showed that the mean mass size was 63.9 mm (range, 25-140 mm). Of 42 patients, 39 were diagnosed (92.8%) after the first biopsy. The accuracy of percutaneous needle biopsy in differentiating between malignant and benign masses was calculated as 90% (36/40).The accuracy of histopathological diagnostic typing as against the postsurgical pathologic examination results was 77.5% (31/40) and the accuracy in the Fuhrman grade was 51.5% (17/33). The sensitivity was calculated as 91.4% and specificity as 60%. Its negative predictive value was 50% and positive predictive value was 94.1%. Conclusions In conclusion, percutaneous renal needle core biopsy has an acceptable sensitivity and specificity in the diagnosis of renal masses. The major limitation of percutaneous core biopsy is the technical failure that leads to insufficient material for accurate diagnosis.

We report a case of epidermoid-cell carcinoma of the lung that developed a metastatic lesion in the penis. A 50-year-old male patient was admitted to our hospital with bloody sputum and cough. He had a left pneumectomy and was diagnosed with epidermoid carcinoma of the lung at stage IIB (T2N1M0). He was started on an adjuvant chemotherapy protocol consisting of cisplatin and paclitaxel. He was admitted to our urology clinic with obstructive symptoms during urination and pain during penile erection. Physical examination revealed a firm, 3 cm x 2 cm palpable mass on the radix of his penis. A fine-needle aspiration biopsy of the penile mass revealed epidermoid carcinoma that was consistent with lung cancer. The patient was considered to have penile metastasis from epidermoid carcinoma of the lung.

Objective The aim of the study was to compare the consistency of major/minor fetal anomalies detected by second trimester prenatal ultrasound examination with the findings in fetal autopsies following the termination of pregnancy (TOP) in the second trimester. Design In a 4-year long prospective study, 107 second-trimester TOP was performed due to fetal malformation diagnosed by second trimester-ultrasound examination at a tertiary referral center. Ultrasound findings were compared with fetal autopsy findings. Result Of the 107 cases with major fetal anomalies diagnosed by prenatal ultrasound, 49% had central nervous system anomalies, 23% had kidney and urinary tract anomalies, 11% had congenital heart disease. All of these major anomalies leading to TOP were confirmed by fetal autopsy (100% success rate in major anomalies). Overall success rate in prenatal ultrasound for major and minor anomalies was 77%. The percentage of additional minor anomalies detected in fetal autopsies was 20%. Three percent of the minor anomalies detected by prenatal ultrasonography could not be confirmed during autopsy. Chromosomal anomalies were detected in 9 (16%) out of 57 cases. Conclusion Evaluation of fetal autopsies following TOP enables diagnosis of pathologies undetected by prenatal ultrasound alone, leading to better preconceptional counseling for subsequent pregnancies. Copyright © 2007 John Wiley & Sons, Ltd.