Lymph node metastases and recurrence in pT1 colorectal cancer: Prediction with the International Budding Consortium Score-A retrospective, multi-centric study.

BACKGROUND: The International Collaboration on Cancer Reporting proposes histological tumour type, lymphovascular invasion, tumour grade, perineural invasion, extent, and dimensions of invasion as risk factors for lymph node metastases and tumour progression in completely endoscopically resected pT1 colorectal cancer (CRC). OBJECTIVE: The aim of the study was to propose a predictive and reliable score to optimise the clinical management of endoscopically resected pT1 CRC patients. METHODS: This multi-centric, retrospective International Budding Consortium (IBC) study included an international pT1 CRC cohort of 565 patients. All cases were reviewed by eight expert gastrointestinal pathologists. All risk factors were reported according to international guidelines. Tumour budding and immune response (CD8+ T-cells) were assessed with automated models using artificial intelligence. We used the information on risk factors and least absolute shrinkage and selection operator logistic regression to develop a prediction model and generate a score to predict the occurrence of lymph node metastasis or cancer recurrence. RESULTS: The IBC prediction score included the following parameters: lymphovascular invasion, tumour buds, infiltration depth and tumour grade. The score has an acceptable discrimination power (area under the curve of 0.68 [95% confidence intervals (CI) 0.61-0.75]; 0.64 [95% CI 0.57-0.71] after internal validation). At a cut-off of 6.8 points to discriminate high-and low-risk patients, the score had a sensitivity and specificity of 0.9 [95% CI 0.8-0.95] and 0.26 [95% 0.22, 0.3], respectively. CONCLUSION: The IBC score is based on well-established risk factors and is a promising tool with clinical utility to support the management of pT1 CRC patients.

Fully Automated Tumor Bud Assessment in Hematoxylin and Eosin-Stained Whole Slide Images of Colorectal Cancer.

Tumor budding (TB), the presence of single cells or small clusters of up to 4 tumor cells at the invasive front of colorectal cancer (CRC), is a proven risk factor for adverse outcomes. International definitions are necessary to reduce interobserver variability. According to the current international guidelines, hotspots at the invasive front should be counted in hematoxylin and eosin (H&E)-stained slides. This is time-consuming and prone to interobserver variability; therefore, there is a need for computer-aided diagnosis solutions. In this study, we report an artificial intelligence-based method for detecting TB in H&E-stained whole slide images. We propose a fully automated pipeline to identify the tumor border, detect tumor buds, characterize them based on the number of tumor cells, and produce a TB density map to identify the TB hotspot. The method outputs the TB count in the hotspot as a computational biomarker. We show that the proposed automated TB detection workflow performs on par with a panel of 5 pathologists at detecting tumor buds and that the hotspot-based TB count is an independent prognosticator in both the univariate and the multivariate analysis, validated on a cohort of n = 981 patients with CRC. Computer-aided detection of tumor buds based on deep learning can perform on par with expert pathologists for the detection and quantification of tumor buds in H&E-stained CRC histopathology slides, strongly facilitating the introduction of budding as an independent prognosticator in clinical routine and clinical trials.

Challenges of the treatment of pediatric hepatosplenic bartonellosis: case report and literature review.

The hepatosplenic (HS) form of cat scratch disease (CSD) is rarely seen; however, management of the treatment is challenging for clinicians. Monotherapy or combination regimens may be preferred based on severity of cases. Along with that, there are uncertainties as to the combination and duration of antibiotics effective against the microorganisms. In this report, a 12-year-old girl diagnosed with HS-CSD and unresponsive to primary treatment with macrolide group antibiotic was presented. The patient had liver findings compatible with CSD, confirmed radiologically and pathologically, and Bartonella henselae indirect immunofluorescence assay IgG was positive at 1/2048 titre. A combination therapy for six months with doxycycline and rifampicin was initiated, and the patient was successfully treated. The preference for monotherapy or combination regimen in HS-CSD is predominantly determined by the clinician according to the severity of the patient's clinical findings. The effectivity of antimicrobial regimen in HS-CSD requires further investigation.

Bone Marrow Necrosis in a Patient Following Blinatumomab Therapy.

Bone marrow necrosis (BMN) is an extremely rare condition characterized by necrosis of the myeloid tissue and medullary stroma leaving an amorphous eosinophilic background and ill-defined necrotic cells in the hematopoietic bone marrow. Several conditions are associated with BMN, including sickle cell disease, metastatic carcinoma, and hematologic malignancies. It is also associated with the use of antineoplastic drugs, such as fludarabine, interferon alpha, and imatinib. Blinatumomab is a CD19/CD3 bispecific T-cell engager antibody which redirects autologous CD3-positive T cells to CD19-positive lymphoblasts creating a cytolytic synapse leading to blastic cells. Cytokine release syndrome, cerebral nervous system toxicities, and febrile neutropenia are the most frequent adverse effects of blinatumomab. Here, we report an adolescent boy with relapse/resistant acute lymphoblastic leukemia developing BMN following blinatumomab therapy. To our knowledge, this is the first case report on BMN following blinatumomab treatment.

A synchronous occurrence of bifocal intracranial germinoma and bilateral testicular epidermoid cyst in an adolescent patient with Klinefelter`s syndrome.

Özyörük D, Kocayozgat A, Yaman-Bajin I, Çetindag F, Oguz- Erdogan AS, Günes A. A synchronous occurrence of bifocal intracranial germinoma and bilateral testicular epidermoid cyst in an adolescent patient with Klinefelter`s syndrome. Turk J Pediatr 2019; 61: 456-459. Klinefelter syndrome (KS) is characterized by an additional X chromosome in males leading to a karyotype of 47,XXY. It is associated with an increased risk of certain malignancies, including leukemia, breast cancer and extragonadal germ cell tumor such as mediastinal germ cell tumors and rarely intracranial germ cell tumors. It is possible that the increased risk of developing certain cancers can be attributed to a direct effect of the chromosomal abnormality or the combined action of the abnormal chromosomes and hormonal imbalances. Here we describe a synchronous occurrence of bifocal intracranial germinoma and bilateral testicular epidermoid cyst in an adolescent patient with Klinefelter`s syndrome. The synchronous occurrence of the dual tumors in this patient with Klinefelter`s syndrome might be resulted from the migration defect during embriyogenesis due to underlying genetic disease or it is a coincidental condition, yet there has been no case reported in the literature, so far.

NUT Midline Carcinoma of the Lung in a Six-Year-Old Child.

BACKGROUND: Nuclear protein of the testis (NUT) midline carcinoma is genetically defined by rearrangement of NUT or by immunohistochemical expression of NUT. FINDINGS: A 6-year old child had a NUT midline carcinoma of the lung. Despite aggressive therapy, the child died. CONCLUSION: NUT carcinoma, which can be diagnosed immunohistochemically, remains an aggressive tumor.

ARID3B expression in primary breast cancers and breast cancer-derived cell lines.

BACKGROUND: ARID3B (AT-rich interaction domain 3) is a member of the family of ARID proteins, which constitutes evolutionarily conserved transcription factors implicated in normal development, differentiation, cell cycle regulation and chromatin remodeling. In addition, ARID3B has been linked to cellular immortalization, epithelial-mesenchymal transition (EMT) and tumorigenesis. Given the emerging role of ARID3B in tumor development, we examined its expression in primary patient-derived breast cancer samples and breast cancer-derived cell lines. METHODS: Immunohistochemistry (IHC) was used to detect ARID3B expression in 63 formalin-fixed paraffin-embedded (FFPE) invasive breast cancer samples. In addition, a panel of 6 (estrogen receptor-positive and -negative, ERBB2-positive and -negative) breast cancer-derived cell lines and immortalized non-tumorigenic epithelial breast cells were used for ARID3B expression analysis using RT-PCR. Specific primers and Western blotting were used to detect ARID3B isoforms. RESULTS: Using IHC, nuclear, cytoplasmic and low levels of membranous ARID3B staining were detected in all 63 primary invasive breast tumors. Nuclear ARID3B staining positively correlated with estrogen receptor (ER) status and negatively correlated with tumor grade, mitotic index and ERBB2 status of the patients. Increased nuclear expression of ARID3B was confirmed in breast cancer-derived cell lines expressing ERα. In addition, two out of three ERBB2-positive breast cancer cell lines were found to lack full length ARID3B. Three ARID3B isoforms were found to be present in normal breast epithelial cells as well as in breast cancer cells. CONCLUSION: We report a positive correlation between ER positivity and nuclear ARID3B expression in primary breast cancers, along with a negative correlation with the ERBB2 status. Very similar correlations were noted in breast cancer-derived cell lines. Since in the recent past ARID3B expression has increasingly been related to cancer-associated proteins and microRNAs, knowledge on ARID3B expression and function may be instrumental for gaining further insight into potentially important cancer-related networks.