Encapsulating peritoneal sclerosis (EPS) is a rare life-threatening complication associated with peritoneal dialysis (PD). EPS is characterized by progressive fibrosis and sclerosis of the peritoneum, with the formation of a membrane and tethering of loops of the small intestine resulting in intestinal obstruction. It is very rare in children. We present a case of a 16-year-old adolescent boy who developed EPS seven years after being placed on continuous ambulatory peritoneal dialysis (CAPD) complicated by several episodes of bacterial peritonitis. The diagnosis was based on clinical, radiological, intraoperative and histopathological findings. The patient was successfully treated with surgical enterolysis. During a 7-year follow-up, there have been no further episodes of small bowel obstruction documented. He still continues to be on regular hemodialysis and is awaiting a deceased donor kidney transplant. EPS is a long-term complication of peritoneal dialysis and is typically seen in adults. Rare cases may be seen in the pediatric population and require an appropriate surgical approach that is effective and lifesaving for these patients.

Dishevelled family proteins (DVL1, DVL2, and DVL3) are cytoplasmic mediators involved in canonical and non‐canonical Wnt signaling that are important for embryonic development. Since Wnt signaling promotes cell proliferation and invasion, its increased activation is associated with cancer development as well. To get deeper insight into the behavior of Dishevelled proteins in cancer, we studied their expression in serous ovarian carcinomas [both low‐ (LGSC) and high‐grade (HGSC)], and HGSC cell lines OVCAR5, OVCAR8, and OVSAHO. DVL protein expression in serous ovarian carcinomas tissues was analyzed using immunohistochemistry, while DVL protein and mRNA expressions in HGSC cell lines were analyzed using Western blot and quantitative real‐time PCR. DVL1 protein expression was significantly higher in LGSC compared with normal ovarian tissue, while DVL3 was overexpressed in both LGSC and HGSC. DVL2 and DVL3 protein expression was higher in HGSC cell lines when compared with normal control cell line FNE1, while DVL1, DVL2, and DVL3 mRNA expression was significantly increased only in OVSAHO cell line. Survival analysis revealed no significant impact of DVL proteins on patients’ outcome. Our data show an active involvement of Dishevelled family proteins in serous ovarian carcinomas. Further studies should confirm the clinical relevance of these observations.

Predatory journals refer to journals that recruit articles through aggressive marketing and spam emails, promising a quick, but not robust, review and fast open-access (OA) publication, thus compromising scholarly publishing standards.1–5 Their key motive is a financial benefit via article processing charges (APCs) and other additional fees.1 3 4 The number of OA journals has dramatically risen over the past 15 years,6 reaching 11 376 journals, indexed in the Directory of Open Access Journals (DOAJ) in 2018 (available at https://doaj.org). This expansion was parallel to the increase in the number of predatory publishers.7 8 Predatory journals have become more prevalent than ever due to massive internet expansion and extensive spam email soliciting.2 4 9 Since 2011, when Jeffrey Beall launched his first list of potential predatory OA publishers and journals, predatory journals have come into focus.3 4 Recent studies have highlighted the significant burden of potentially predatory journals in several biomedical specialties, including neuroscience/neurology, urology, emergency medicine, physical medicine, orthopaedics, rehabilitation, as well as anaesthesiology.7 8 10–13 No study on predatory journals in pathology has been conducted so far. As previously suggested, we explored Beall’s list of predatory journals as an initial database of suspected journals related to pathology.2 8 The term predatory was only applied after assessing each journal separately. The assessment was based on the recommended …

Metastatic Leydig cell tumors (LCT) are rare, difficult to treat malignancies without known underlying molecular-genetic events. We profiled 27 LCT cases using NGS and immunohistochemistry. Our study identified TERT gene fusions as a main genetic alteration and a potential therapeutic target in LCT. TOP1 and AR expressions may guide decisions on chemo- and/or hormone therapy for selected individual patients. Objective: Metastatic Leydig cell tumors (LCT) are rare, difficult-to-treat malignancies without known underlying molecular–genetic events. An index case of metastatic LCT showed an LDLR–TERT gene fusion upon routine genetic profiling for detection of therapeutic targets, which was then followed by an investigation into a cohort of additional LCTs. Patients and Methods: Twenty-nine LCT (27 male and 2 female patients) were profiled using next-generation sequencing and immunohistochemistry. Results: TERT gene fusions were detected only in testicular metastatic LCTs, in 3 of 7 successfully analyzed cases (RMST:TERT,LDLR:TERT, and B4GALT5:TERT). TOP1 and CCND3 amplifications were identified in the case with a B4GALT5:TERT fusion. A TP53 mutation was detected in 1 metastatic tumor without a TERT fusion. Five primary (4 testicular and 1 ovarian) LCTs showed multiple gene amplifications, without a consistent pattern. A single metastatic ovarian LCT showed BAP1 mutation and copy number amplifications affecting the NPM1, PCM1, and SS18 genes. At the protein level, 4 of 7 metastatic and 6 of 10 primary testicular LCTs overexpressed Topo1. Androgen receptor was overexpressed in 10 of 13 primary testicular tumors and 2 of 5 metastatic testicular LCTs (without detectable ARv7 messenger RNA or ARv7 protein). Only 1 metastatic testicular LCT exhibited a high tumor mutational burden; all tested cases were microsatellite instability stable and did not express programmed cell death ligand 1. Conclusions: Our study for the first time identified TERT gene fusions as a main genetic alteration and a potential therapeutic target in metastatic LCTs. Topo1 and androgen receptor may guide decisions on chemotherapy and/or hormone therapy for selected individual patients.

Abstract Background An optimal adjuvant treatment of HER2 positive breast cancer includes the initiation of trastuzumab within 6 months after the surgery. However, due to limited resources and waiting lists, this timeframe is often exceeded in developing countries. We previously reported short-term outcomes of a time-optimal versus delayed postoperative initiation of trastuzumab in women with HER2 positive, non-metastatic, neoadjuvant naive breast cancer. Here, we report an extended follow-up, summarizing outcomes of our cohorts. Methods We included 223 consecutive women with surgically treated, non-metastatic, neoadjuvant naive, HER2 positive breast cancer from 2009 to 2011, from four institutions in Bosnia and Herzegovina. Patients were assigned to a time-optimal group (TOG), or a delayed group 1 (DG1), or a delayed group 2 (DG2), depending on whether their adjuvant trastuzumab was initiated 6 months, or 6-12 months, or more than 12 months after the surgery, respectively. A cut-off point for the follow-up was January 2019. We compared clinical outcomes between the groups, taking into account lymph node status. Results The patient’s median age was 55 (range 27-80) years. Mean follow-up period was 67 (range 4-109) months. Node-negative disease was found in 38.6% patients overall. 37% (TOG) patients received trastuzumab within 6 months, while 41% (DG1) received it within 6-12, and 22% (DG2) more than 12 months after their surgery. A higher number of node negative patients was found in the DG2 group compared to the TOG and DG1 groups (48%, 35%, and 36% respectively). 5-year DFS rate was 70.73% (TOG), 67.03% (DG1), and 62.00% (DG2). The OS rate was 78.05% (TOG), 75.82% (DG1), and 74.00% (DG2). Conclusions From the above, a conclusion can be made that patients with time-optimal initiation of adjuvant trastuzumab therapy had a higher 5-year DFS and OS rate compared to the delayed treatment initiation groups. Results of the DG1 and the DG2 group indicate that trastuzumab therapy shows a persistent benefit even if administered with a delay. Higher DFS and OS rates in the DG2 group could be explained by a higher number of node-negative low-risk, patients in this group. Legal entity responsible for the study The authors. Funding Roche. Disclosure S. Beslija: Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: MSD; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer. T. Ceric: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: MSD; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis. B. Hasanbegovic: Advisory / Consultancy: Roche. A. Pasic: Advisory / Consultancy: Merck; Advisory / Consultancy: Sanofi. All other authors have declared no conflicts of interest.

Aim Barrett’s esophagus (BE) is a predisposing factor of esophageal adenocarcinoma/gastroesophageal junction adenocarcinoma (ECA/GEJ Aca). BE patients are stratified and subsequently monitored according to the risk of malignant progression by the combination of endoscopy and biopsy. This study is to evaluate the maspin expression patterns as early diagnostic markers of malignancy in BE patients. Materials and methods Immunohistochemistry (IHC) staining was performed on 62 archival core biopsies from 35 patients, including BE without dysplasia (intestinal metaplasia, IM), BE with low grade dysplasia, BE with high grade dysplasia, carcinoma in situ, and well to poorly differentiated ECA/GEJ Aca (PD-ECA/GEJ Aca). The intensity and the subcellular distribution of immunoreactivity were evaluated microscopically. Statistical analysis was performed using the χ2 and Fisher exact tests. Results The level of epithelial-specific tumor suppressor maspin protein inversely correlated with the progression from IM to PD-ECA/GEJ Aca. Lesions of each pathological grade could be divided into subtypes that exhibited distinct maspin subcellular distribution patterns, including nuclear only (Nuc), combined nuclear and cytoplasmic (Nuc+Cyt), cytoplasmic only (Cyt) and overall negligible (Neg). The Cyt subtype, which was minor in both IM and dysplasia (approximately 10%), was predominant in ECA/GEJ Aca as early as well-differentiated lesions (more than 50%: p = 0.0092). In comparison, nuclear staining of the tumor suppressor TP53 was heterogeneous in dysplasia, and did not correlate with the differentiation grades of ECA/GEJ Aca. Conclusion The Cyt subtype of maspin expression pattern in core biopsies of BE patients may serve as a molecular marker for early diagnosis of ECA/GEJ Aca.

Dear Editor, We highly appreciate Dr Altundag's feedback regarding our recently published manuscript in The Breast Journal.1 We are also thankful to the editor in chief (Dr S. Masood) for giving us the opportunity to address Dr Altundag's comments. Neo‐adjuvant chemotherapy has been widely used for breast cancer treatment due to the effective pathologic responses seen with newer therapeutic agents.2 Recently, it has also been introduced for the treatment of early breast cancer.3 Despite this, there is ongoing debate and controversies related to the use of neo‐adjuvant chemotherapy in breast cancer (critically appraised in a recent review by Vaidya et al2). We find Dr Altundag's point regarding our neo‐adjuvant cohort quite valid. In our study, ~43% of patients with invasive apocrine carcinoma (IAC) presented at the advanced stage (III or IV) with only 19% of the patients having the tumor size ≤2 cm at presentation. This is mainly due to the lack of organized screening program at the national level. In this regard, our small IAC cohort treated in neo‐adjuvant setting is somehow biased but it essentially reflected the previous and current overall breast cancer presentation in Bosnia and Herzegovina. Consequently, the response rates to neo‐adjuvant therapy in our study may be different from the previously published data. Noteworthy, IAC is a rare breast cancer subtype (~1%‐2% of all breast cancers)4,5 and future larger and multi‐institutional studies are required to validate the effectiveness of (neo)adjuvant chemotherapy in patients with IAC.

Neuroendocrine breast cancer (NEBC) is a group of rare tumors, which could benefit from therapy targeting the somatostatin receptors (SSTRs). In particular, SSTR2A and SSTR5 are potential targets given their consistent expression in gastrointestinal and pancreatic primary and metastatic neuroendocrine cancers. Currently, there are no studies describing the expression of SSTRs in NEBC. The purpose of our study was to characterize the immunohistochemical expression of SSTR2A and SSTR5 in a cohort of NEBC. Thirty-one primary NEBC cases were analyzed, and SSTR2A and SSTR5 immunohistochemistry performed and scored using the modified immunoreactive score proposed by Remmele and Stanger. All patients were females with a mean age of 66.6 years (SD = 14). 77% of cases were histological grade 2. SSTR2A showed a weak positivity in 11 cases (35.5%), moderate positivity in 6 cases (19.4%) and strong positivity in 5 cases (16.1%). Nine cases were negative for SSTR2A (29%). SSTR5 showed a weak positivity in 16 cases (51.6%), moderate positivity in 6 cases (19.4%), while no cases showed strong positivity. Nine cases were negative for SSTR5 (29%). Five cases were negative for both SSTR2A and SSTR5. A weak to moderate SSTR2A and SSTR5 expression was observed in 50-70% of the cases. A subset of NEBCs with strong SSR2A expression may benefit from SSTRs targeted therapy. These results need further validation in a larger series including metastatic NEBC, to provide potential therapeutic targets for patients with advanced disease.

Clear cell renal cell carcinoma (ccRCC), the most common histologic subtype of RCCs, demonstrates a wide spectrum of morphologic features (i.e., low-grade spindle cell, syncytial giant cells, and mucin-producing cells). However, papillary growth pattern in ccRCCs is rather a rare finding, which can present challenges in differential diagnostic work up. The aim of this study was to investigate ccRCCs with predominant papillary features from morphologic, immunohistochemical and molecular genetic perspectives. 23 clear cell renal cell carcinomas with papillary architecture were selected. Tumors were evaluated morphologically, immunohistochemically, and molecularly by next-generation sequencing (NGS). The diagnosis of MiT family translocation RCC was excluded by TFE3 immunohistochemistry. Mean age of patients was 65.2 years (range 42-81 years), and 19/23 were male. Tumor size ranged from 1.6 to 12.8 cm (median 6.5 cm). At a median follow-up of 2.5 years (range 1.5-9 years), 2 patients (8.7%) died of disease, 2 developed metastasis. Areas of papillary pattern accounted for approximately 40-100% of the tumor. CK7 was negative in non-papillary areas in majority of cases (20/23, 87%), and was only focally positive in 3/23 cases (13%). In papillary areas, AMACR was positive/focally positive in 17/23 (73.9%) cases and in the non-papillary areas it was positive/focally positive in 22/23 (95.6%) cases. CAIX was mainly negative in both non-papillary and papillary areas (15/23 [65%] and 16/23 [69.5%], respectively). Molecular analysis of 15 analyzable cases revealed the most frequently mutated gene to be VHL (in 9 cases), followed by PRBM1 (in 2 cases) and 29 other different mutations in various genes. Papillary growth pattern in ccRCC is not an uncommon situation. Papillary RCC with clear cells and MiT family (TFE3) translocation RCCs are the major differential diagnostic considerations in such scenarios. Our NGS molecular analysis supported classifying such tumors as a morphologic variant of ccRCC.

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.

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