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Objective: We present a 17-year-old boy with an incidentally diagnosed left adrenal ganglioneuroma during the diagnostic workup of alopecia areata. Clinical Presentation and Intervention: Laboratory investigations revealed vitamin D deficiency. Laparoscopic adrenalectomy was performed and ganglioneuroma was confirmed histologically. At follow-up, the vitamin D supplements improved the vitamin D levels followed by a gradual regression of alopecia areata. However, it recurred 18 months later despite the normal levels of serum vitamin D and no tumor recurrence. Conclusion: Further studies should reveal the relationship between alopecia areata and ganglioneuroma as well as the role of vitamin D in alopecia areata.

I. Gupta, Rasha M. Sareyeldin, Israa Al-Hashimi, Hamda A. Al-Thawadi, Halema F Al Farsi, S. Vranić, A. Al Moustafa

Breast cancer is the most frequent cause of cancer-related deaths among women worldwide. It is classified into four major molecular subtypes. Triple-negative breast cancers (TNBCs), a subgroup of breast cancer, are defined by the absence of estrogen and progesterone receptors and the lack of HER-2 expression; this subgroup accounts for ~15% of all breast cancers and exhibits the most aggressive metastatic behavior. Currently, very limited targeted therapies exist for the treatment of patients with TNBCs. On the other hand, it is important to highlight that knowledge of the molecular biology of breast cancer has recently changed the decision-making process regarding the course of cancer therapies. Thus, a number of new techniques, such as gene profiling and sequencing, proteomics, and microRNA analysis have been used to explore human breast carcinogenesis and metastasis including TNBC, which consequently could lead to new therapies. Nevertheless, based on evidence thus far, genomics profiles (gene and miRNA) can differ from one geographic location to another as well as in different ethnic groups. This review provides a comprehensive and updated information on the genomics profile alterations associated with TNBC pathogenesis associated with different ethnic backgrounds.

Shaikha S Al-Qahdi, Nada Alzohari, Abrar Y Alsaid, Anas A Ashour, Tahar Aboulkassim, S. Vranić, A. Al Moustafa, Ashraf Khalil

The aim of this study is to explore the outcome of Teucrium polium (TP) medicinal plant consumption on the early stage of fetal development. We used the chicken embryo at 3 days of incubation as a model to evaluate the effect of TP plant extract during embryogenesis. In addition, quantitative polymerase chain reaction (qPCR) was applied to explore the expression of six genes related to cell proliferation, apoptosis, sur-vival, angiogenesis, and migration. Our data revealed that TP exposure inhibits angiogenesis of the chicken embryo and its chorioallantoic membrane. In addition, we found that TP extract significantly harms the normal development of the embryos since around 95% of TP-exposed embryos died after 1-3 days of treatment. Macroscopic examination did not show any anomalies in these embryos. However, qPCR analysis of activation transcription factor-3, B-cell lymphoma-2, caspase 8, inhibin subunit beta A, vascular endothelial growth factor-C, and Cadherin-6 type-2 genes revealed that these genes are considerably deregulated in heart and brain tissues from TP-exposed embryos in comparison with their matched tissues from unexposed ones. Our study implies that TP plant can have very toxic effects on the early stage of the embryo. Therefore, it is important to alert expectant women to avoid the use of this medicinal plant during pregnancy.

Gastric necrosis with perforation is a rare and potentially life-threatening condition in childhood beyond the neonatal period. We report a case of gastric necrosis and perforation of a portion of the great curvature due to a massive gastric dilatation caused by pathological aerophagia in a 13-years-old, mentally impaired adolescent girl. Despite the successful surgical treatment, the patient's condition rapidly deteriorated post-operatively and she died due to the multisystem organ failure and multiple infections. In addition, we surveyed the literature on this rare condition and assessed the preventive actions to reduce this life-treating condition.

Z. Zvizdic, E. Milisic, Adisa Chikha, I. Sefić, Amra Džananović, S. Vranić

Rationale: Hydrocele of the canal of Nuck is a rare developmental disorder and represents of a homolog of hydrocele of spermatic cord in males. Hydrocele of the canal of Nuck is a very rare cause of inguinal swelling in female infants and children. It results from the failure of obliteration of the distal portion of evaginated parietal peritoneum within the inguinal canal, which forms a sac containing fluid. Patient concerns: We describe a case of hydrocele of the canal of Nuck in an 11-month-old girl with a past medical history of duodenal atresia and Arnold-Chiari malformation. Diagnosis: Physical examination and ultrasound revealed a soft, cystic, noncompressible, and non-fluctuant labial mass measuring approximately 5 cm. Interventions: The patient underwent surgical exploration through a right skin crease incision. The cystic lesion was histologically confirmed to be a non-communicated hydrocele of canal of Nuck. Outcomes: The child is doing well at 1-year follow-up with no swelling or recurrence on the operated side. Lessons: Hydrocele of the canal of Nuck is a rare developmental disorder but should be considered in a differential diagnosis in young girls with an inguino-labial swelling.

S. Vranić, J. Palazzo, J. Swensen, J. Xiu, Elena Florento, Z. Gatalica

Pleomorphic ductal carcinoma (PDC) is a very rare subtype of invasive ductal carcinoma of no‐special type (NST), characterized by the presence of highly atypical/bizarre (>6‐fold variation in nuclear size) and multinucleated (giant) neoplastic cells comprising >50% of the tumor cell population (Figure 1A). PDC is typically triple‐negative breast cancer (TNBC), associated with an aggressive clinical course and a poor outcome.2–4 So far, no single study explored novel predictive biomarkers for the precision medicine purposes in the patients with PDC. Formalin‐fixed paraffin‐embedded tissue samples of the six PDC patients (four primary and two metastatic cases) were sequenced for 592‐genes using NextSeq platform (Illumina, La Jolla, CA, USA). Tumor mutational load (TML) was calculated using only somatic nonsynonymous missense mutations; high TML was considered when it was ≥17 mutations/Mb. Microsatellite instability (MSI) status was explored by the direct analysis of known MSI loci in the target regions of the sequenced genes. Cases were considered microsatellite instable (MSI‐H) if they exhibited ≥46 altered microsatellite loci (the threshold was established by comparing to the PCR‐based MSI FA result from ~2100 cases). Copy number variations (CNVs) were determined by comparing the depth of sequencing of genomic loci with a diploid control. Calculated gains ≥6 copies were considered amplified. ArcherDx FusionPlex Assay was used to detect gene fusions (52 gene targets). Immunohistochemistry was used to detect expression of PD‐L1 (SP142 antibody, Ventana) in tumor cells (TC) and immune cells (IC). PD‐L1 positivity in TC was defined as 2+ intensity in ≥5% of tumor cells. PD‐L1 status

Yaman M AlAhmad, I. Abdelhafez, F. Cyprian, F. Skenderi, S. Akhtar, S. Vranić

Predatory or pseudo journals have recently come into focus due to their massive internet expansion and extensive spam email soliciting. Recent studies explored this urging problem in several biomedical disciplines. In the present study, we identified 69 potential predatory (pseudo) pathology journals that were contrasted to 89 legitimate pathology journals obtained from the major bibliographic databases. All potential predatory journals in pathology shared at least one of the features proposed by previous studies (e.g. a poor web-site integrity, submissions via email, unclear or ambiguous peer-review process, missing names of the editorial board members, missing or pending the journal ISSN). Twenty-one (30%) of the potential predatory pathology journals had misleading titles mimicking those of legitimate journals. Only one of the identified journals was listed in the Directory of Open Access journals whereas none (0%) was indexed in PubMed/MEDLINE or Web of Science, listed in the Committee on Publication Ethics nor have they had a legitimate impact factor in the Journal Citation Reports.

S. Bedri, A. Sultan, M. Alkhalaf, A. Al Moustafa, S. Vranić

ABSTRACT Epstein-Barr virus (EBV) is a well-characterized oncovirus, associated with several malignancies. The complex and heterogeneous nature of colorectal cancer (CRC) has led to many epidemiological causal associations with CRC. However, a direct causal link between microbial infections and CRC has not been established yet. Our review indicates that the current evidence for the presence and role in EBV in CRC is insufficient and contradictory. The design of the analyzed studies, sample size as well as methodology used for EBV detection varied markedly and consequently may not lead to meaningful conclusions. The presence of EBV in other colorectal tumors (lymphomas, smooth muscle tumors) is in line with their status at other anatomic locations and may have therapeutic implications with EBV-specific vaccines. On the other hand, studies exploring EBV in colorectal adenoma-carcinoma sequence and its molecular genetic characteristics are largely missing and may significantly contribute to a better understanding of the role of EBV in CRC.

Khaled W. Sadek, Mahmoud Y. Haik, Anas A Ashour, Tahira Baloch, Tahar Aboulkassim, A. Yasmeen, S. Vranić, A. Zeidan et al.

Jasenka Zmijanac Partl, Valentina Karin, A. Škrtić, Tamara Nikuševa‐Martić, A. Šerman, J. Mlinarec, M. Ćurković-Perica, S. Vranić et al.

Abstract Objective: Since Wnt signaling pathway plays a pivotal role in the placental development, we explored the expression of its negative regulators, SFRP1 and SFRP3 proteins in placentas from pathological pregnancies and compared their levels with those in healthy placentas. Methods: Placentas (n = 79) were stained for SFRP1, and SFRP3 proteins by immunohistochemistry and their expression levels were quantified by stereological variable of volume density (Vv, mm°). Results: Significantly higher expressions of SFRP1 and SFRP3 were found in all investigated groups of term and preterm pathologic placentas as well as in preterm control placentas in comparison with normal-term placentas. Conclusions: Our findings indicate the active involvement of negative Wnt regulators SFRP1/SFRP3 in placental development and important role in pathology of pregnancy.

Denira Imamovic, N. Bilalović, F. Skenderi, V. Bešlagić, T. Cerić, Berisa Hasanbegović, S. Bešlija, S. Vranić

School of Medicine, University of Sarajevo, Sarajevo, Bosnia and Herzegovina Department of Pathology, Clinical Center, University of Sarajevo, Sarajevo, Bosnia and Herzegovina Department of Radiology, Clinical Center, University of Sarajevo, Sarajevo, Bosnia and Herzegovina Department of Oncology, Clinical Center, University of Sarajevo, Sarajevo, Bosnia and Herzegovina College of Medicine, Qatar University, Doha, Qatar

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