A congenital hernia into the umbilical cord (CHUM) is often misinterpreted as a mild form of omphalocele. Herniated content in CHUM can be either the solitary intestinal loop or persistent omphalomesenteric duct (POMD) with the potential for traumatic injury in a case of inadequate examination of the umbilical cord and its clamping in the delivery room. Herein, we report a case of a male newborn with a functional bowel obstruction due to peritonitis caused by necrosis of iatrogenically clamped POMD in the CHUM. A 2-day-old full-term male infant was referred to the emergency department with a 1 day history of bilious vomiting, a gradual increase in abdominal distension, and absence of passage of meconium. The infant was born at 38 weeks’ gestation with a birthweight of 2,885 g. The baby was born following an uncomplicated pregnancy and a normal spontaneous vaginal delivery. The Apgar scores were eight at both 1 and 5 min. On physical examination, his abdomen was slightly distended by an umbilical ligation clip placed approximately 2.5 cm from the enlarged base of the umbilical cord (Fig. 1a). The stump of the umbilical cord was thickened and red. The baby was pale and dehydrated. An abdominal radiograph showed dilated small bowel loops due to small bowel obstruction (Fig. 1b). After resuscitation, a surgical exploration via a circumumbilical incision revealed a clamped POMD in the umbilical cord. The top of the POMD was crushed by the umbilical cord clamp (Fig. 1c). The POMD was resected at its base on the ileal loop. The ileal loop was closed transversely using 5-0 Vicryl by single-layer extra mucosal-interrupted sutures. The postoperative recovery was uneventful at a follow up of 8 years. Evaluation of the umbilical cord is a routine part of every newborn examination in the delivery room. Any suspected abnormal thickening of the base of the umbilical cord or any other malformations found should be further evaluated by a neonatologist or pediatric surgeon. Congenital hernia into the umbilical cord is a type of ventral abdominal wall defect in which the bowel usually herniates into the base of normally inserted umbilical cord through a patent umbilical ring. The condition results from a failure of return of intestine loops following the physiological gut herniation around 10–12 weeks of gestation. Due to similar morphologic features, characterized by coverage of eviscerated abdominal contents with a sac comprising outer amnion and inner peritoneal lining, CHUM may be easily misdiagnosed as a small omphalocele. Unlike an omphalocele, CHUM has an intact abdominal wall with adequate muscle development and a complete umbilical ring covered by a small cuff of skin about ~2.5 cm. Congenital hernia into the umbilical cord is usually not linked to chromosomal abnormalities but cases of trisomy 13 associated with CHUM have been reported in the literature. However, if missed, this condition can lead to intestinal damage by a low-placed umbilical cord clamp as it is shown in our illustrative case. Although very rare, similar complications have been reported in the literature. The prevention of inadvertent bowel injury during cord clamping at delivery is possible with increased awareness and knowledge regarding CHUM. Primary prevention includes the prenatal sonographic CHUM detection characterized by intestinal protrusion only into the base of the hernia. The most important preventive measure if the umbilical cord is broad based is the umbilical cord clamping at a safe distance from the basis (at least 5 cm from the abdominal wall). In conclusion, a careful inspection of the umbilical cord of all newborns in the delivery room is essential to identify any clinically relevant umbilical abnormality (e.g., a persistence of CHUM with POMD). This would prevent any iatrogenic gut injury during umbilical cord clamping. Although these complications are rare, they should be kept in mind when performing umbilical cord clamping.

Abstract Rationale: Pentalogy of Cantrell (POC) is an extremely rare syndrome with an estimated incidence of 1:65,000 to 200,000 live births. Its complete form includes a midline epigastric abdominal wall defect, defects affecting the lower sternum, anterior diaphragm, diaphragmatic pericardium, and various intracardiac defects. Patient concerns: We report a case of complete POC affecting only the first-born of a set of premature dizygotic twins. Diagnosis: A giant omphalocele with an eviscerated liver and bowel on prenatal, obstetric ultrasonography at 24 gestational weeks was observed. At birth, physical examination confirmed a massive (10 × 8 cm) epigastric omphalocele in which a significant part of the liver was seen. A postnatal echocardiogram revealed the presence of an ostium secundum atrial septal defect, perimembranous ventricular septal defect, and moderate pulmonary stenosis. X-ray showed an abnormal intrathoracic positioned stomach, which was confirmed with a plain x-ray of the upper intestinal tract with hydrosoluble contrast. Computed tomography (CT) scan revealed the sternum's absence and a close connection between the pericardial sac and the stomach wall. Interventions: The patient underwent surgical intervention at 18 days of age. Outcomes: Despite adequate and appropriate postoperative treatment, the baby rapidly deteriorated and died 72 hours after surgery. Lessons: POC is a complex, high-mortality syndrome whose management requires a multidisciplinary approach and meticulous planning. Despite all efforts, POC carries a poor prognosis, particularly in patients affected by its complete form.

A 65-year-old woman with a negative family history of breast cancer presented with a palpable mass in the left breast’s central portion. Mammography revealed an oval heteroechogenic, partly solid, partly cystic, sharply demarcated mass, measuring 100×90 mm in greatest diameter, classified as BI-RADS 4c, according to ACR BI-RADS Atlas Fifth Edition (Figure 1A-B). Breast MRI showed a lobulated mass with smooth margins appearing hypointense on T1WI and high signal intensity on T2WI (Figure 1C-D). A core needle biopsy revealed a cellular neoplasm, composed of small, closely packed tubules with spindle cell intervening stroma without prominent atypia and mitotic activity, classified as B3 category according to the UK National Coordinating Committee for Breast Screening Pathology (Figure 2A). The multidisciplinary tumor board discussed the case and recommended a wide surgical excision. With the patient’s approval, a left mastectomy was recommended and performed. The axillary clearance was not performed. The 100×90 mm tumor was grossly well-circumscribed, grayish-white, and predominantly solid, with a smaller cystic component, without necrosis and hemorrhage (Figure 2B). Histopathologic examination revealed a well-circumscribed tumor with two distinct components (tubular adenoma and phyllodes tumor) with the transition to one another (Figure 2C). The larger portion of the tumor was composed of closely packed small round to oval tubules with little intervening spindle cell stroma consistent with tubular adenoma. The smaller component showed a biphasic fibroepithelial tumor with leaf-like projections with moderately cellular stroma (Figure 2D-E). The stromal cells exhibited mild to moderate atypia, and their mitotic activity was up to six mitoses/10 hpf (Figure 2F). Stromal overgrowth was absent, while the malignant heterologous elements were not observed despite the exhaustive tumor sampling (25 paraffin blocks). The final diagnosis was a complex fibroepithelial tumor composed of borderline phyllodes and tubular adenoma. Clinical Science

This review provides a brief overview of the state-of-the-art molecular pathology approaches emphasizing the increasingly important pathology role in clinical precision cancer medicine. Recent advances in molecular biology and genetics have tremendously affected the practice of anatomic pathology, gradually transforming it from a morphology-based into a molecularbased discipline. Molecular diagnostics has a long tradition in pathology, especially in clinical pathology. The improvement of methodology for genomic testing in recent years has made it one of the cornerstones of precision cancer medicine. The decisions related to cancer treatments are no longer solely based on the histopathological diagnosis. Various genomic analyses of human cancers are being incorporated into diagnostic and decision-making algorithms. CONCLUSION: The pathologists continue to play an essential role in developing and implementing molecular and genomic tests in practice and communicate the results and their relevance with clinicians. Such activities are of utmost importance for successfully translating scientific advancements into a benefit to patients ("next-generation pathologists").

Breast cancer is a leading cause of death in women around the world. Most breast cancer-related deaths are a result of complications from the metastatic spread. Several recent studies reported that high-risk human papillomaviruses (HPVs) and Epstein–Barr virus (EBV) are co-presented in different types of human carcinomas including breast; however, the cooperative effects between high-risk HPVs and EBV oncoproteins in human breast cancer have not been investigated yet. Thus, we herein explored the cooperation outcome between E6/E7 and latent membrane protein 1 (LMP1) oncoproteins of high-risk HPV type 16 and EBV, respectively, in two human breast cancer cell lines, MCF7 and MDA-MB-231. Our data revealed that the cooperation of E6/E7 and LMP1 oncoproteins stimulates cell proliferation and deregulates cell cycle progression of human breast cancer and normal mammary cells; in parallel, we noted that E6/E7/LMP1 incite colony formation of both breast cancer cell lines but not normal cells. More significantly, our results point out that the co-expression of E6/E7 and LMP1 oncoproteins enhances cell motility and invasion of MCF7 and MDA-MB-231 cell lines; this is accompanied by deregulation of epithelial–mesenchymal transition biomarkers including E-cadherin, β-catenin, fascin, and vimentin. The molecular pathway analysis of HPV and EBV oncoproteins cooperation shows that it can enhance the phosphorylation of extracellular signal-regulated kinases (Erk1/Erk2) in addition to β-catenin, which could be behind the effect of this cooperation in our cell models. The study clearly suggests that high-risk HPV and EBV coinfection can play an important role in breast cancer progression via Erk1/Erk2 and β-catenin signaling pathways.

Abstract Rationale: Pheochromocytoma (PHEO) is a rare neuroendocrine tumor arising from chromaffin cells of the adrenal medulla. Most pediatric PHEOs are functional tumors, and clinical manifestations are related to catecholamine hypersecretion and/or tumor mass effects. Patient concerns: We report here a case of a 10-year-old boy with a highly functional adrenal PHEO detected after the evaluation of a generalized tonic-clonic seizure in the patient. His vital signs at admission were: blood pressure up to 220/135 mm Hg; pulse, 112 beats/min; temperature, 37.4°C; respiratory rate, 22 breaths/min. Diagnosis: A 24-hour urine collection for catecholamines test showed a marked increase in Vanillylmandelic acid levels (338.9 μmol/L). An abdominal magnetic resonance imaging revealed a well-defined left adrenal gland mass measuring ∼5 cm in its largest dimension. Interventions: The mass was surgically removed, and histopathological examination revealed PHEO with low malignant potential (Adrenal Gland Scaled Score/PASS/ < 4). Outcomes: The patient was discharged on the 10th postoperative day in good condition. At 24-month follow-up, the patient was doing well without complications such as tumor recurrence, elevated blood pressure, and seizure. Lessons: PHEO should be considered in the differential diagnosis of children with seizures presenting in the emergency department. A multidisciplinary approach to the evaluation and treatment of PHEO is also crucial for a successful outcome.

INTRODUCTION Gastric acidity plays an important role in the protection of infants against various pathogens from the environment. The histamine-2 receptor blockers (H2-blockers) are off-labeled drugs that are frequently prescribed in preterm neonates to prevent stress ulcers. The impact of the H2-blockers on the development of the necrotizing enterocolitis (NEC) in preterm infants is still controversial, particularly in the developing world. MATERIALS AND METHODS One hundred twenty-two preterm infants were enrolled in the study. The multivariate logistic regression model was used to identify potential postnatal risk factors associated with NEC. RESULTS Preterm infants (n = 51) with total NEC, medical NEC, and surgical NEC had the highest rate of receiving ranitidine compared with controls (n = 71) (39.2%, 19.6%, and 47.6%, p < 0.05). Logistic regression analysis revealed that ranitidine use and nosocomial infections were significantly associated with NEC development (odds ratios 1.55 and 3.3). CONCLUSIONS We confirm that ranitidine administration was associated with an increased risk of NEC in preterm infants. H2-blockers use should be only administered in very strictly selected cases after careful consideration of the risk-benefit ratio.

Antibody-drug conjugates represent a new class of highly potent antineoplastic drugs built by attaching a small molecule of an anticancer drug (payload) or another therapeutic agent to an antibody recognizing an epitope on the targeted cells. Trophoblast cell-surface antigen-2 (Trop-2) was originally described in trophoblasts and fetal tissues, but subsequently its overexpression has been demonstrated in various solid malignancies. Sacituzumab govitecan (SG), a conjugate of anti-Trop-2 antibody and SN-38 payload (an active metabolite of irinotecan), is the first in the class that has been clinically validated and approved by the Food and Drug Administration for the treatment of metastatic triple-negative breast (2020) and urothelial carcinomas (2021). In the current review, we summarize and critically appraise the most recent advances with regard to SG, emphasizing the predictive biomarker analysis.

Dishevelled family proteins (DVL1, DVL2, and DVL3) are cytoplasmic proteins that are involved in canonical and non-canonical Wnt signaling pathway during embryonic development. The role of DVL proteins in the placental tissue remains mostly unknown. In the current study, we explored the role of Dishevelled proteins in naturally invasive tissue, trophoblast. Formalin-fixed paraffin-embedded samples of 15 term placentas from physiologic term pregnancies and 15 term placentas from pregnancies complicated with intrauterine growth restrictions (IUGR) were used for the study. Expression levels of mRNA for DVL1, DVL2, and DVL3 in placentas were analyzed by quantitative real-time PCR (qRT-PCR). DVL1, DVL2, and DVL3 protein expression were semi-quantitatively analyzed using immunohistochemistry. The expression of DVL3 protein was significantly higher in trophoblasts and endothelial cells in placental villi from IUGR pregnancies compared with the control group of term placentas, while DVL2 protein expression was significantly higher in trophoblasts in placental villi from IUGR pregnancies compared with normal term placentas. The observed differences at protein levels between normal and IUGR placentas were not confirmed at the mRNA levels of DVL genes. Our data indicate the active involvement of DVL proteins in IUGR-related placentas. No significant changes were observed in DVL mRNA levels between the two groups of placentas. Further studies are required to explore the clinical relevance of these observations.

Dishevelled family proteins (DVL1, DVL2, and DVL3) are cytoplasmic proteins that are involved in canonical and non-canonical Wnt signaling pathway during embryonic development. The role of DVL proteins in the placental tissue remains mostly unknown. In the current study, we explored the role of Dishevelled proteins in naturally invasive tissue, trophoblast. Formalin-fixed paraffin-embedded samples of 15 term placentas from physiologic term pregnancies and 15 term placentas from pregnancies complicated with intrauterine growth restrictions (IUGR) were used for the study. Expression levels of mRNA for DVL1, DVL2, and DVL3 in placentas were analyzed by quantitative real-time PCR (qRTPCR). DVL1, DVL2, and DVL3 protein expression were semi-quantitatively analyzed using immunohistochemistry. The expression of DVL2 and DVL3 proteins was significantly higher in trophoblasts in placental villi from IUGR pregnancies compared with the control group of term placentas. In contrast, DVL3 protein expression was significantly higher in endothelial cells in placental villi from IUGR pregnancies compared with normal term placentas. The observed differences at protein levels between normal and IUGR placentas were not confirmed at the mRNA levels of DVL genes. Our data indicate the active involvement of DVL proteins in IUGR-related placentas. No significant changes were observed in DVL mRNA levels between the two groups of placentas. Further studies are required to explore the clinical relevance of these observations.

Colorectal cancer (CRC), the third most common type of cancer, is the second leading cause of cancer-related mortality rates worldwide. Although modern research was able to shed light on the pathogenesis of CRC and provide enhanced screening strategies, the prevalence of CRC is still on the rise. Studies showed several cellular signaling pathways dysregulated in CRC, leading to the onset of malignant phenotypes. Therefore, analyzing signaling pathways involved in CRC metastasis is necessary to elucidate the underlying mechanism of CRC progression and pharmacotherapy. This review focused on target genes as well as various cellular signaling pathways including Wnt/β-catenin, p53, TGF-β/SMAD, NF-κB, Notch, VEGF, and JAKs/STAT3, which are associated with CRC progression and metastasis. Additionally, alternations in methylation patterns in relation with signaling pathways involved in regulating various cellular mechanisms such as cell cycle, transcription, apoptosis, and angiogenesis as well as invasion and metastasis were also reviewed. To date, understanding the genomic and epigenomic instability has identified candidate biomarkers that are validated for routine clinical use in CRC management. Nevertheless, better understanding of the onset and progression of CRC can aid in the development of early detection molecular markers and risk stratification methods to improve the clinical care of CRC patients.