Abstract Malignant peritoneal mesothelioma is an extremely rare and poorly recognized neoplasm in children. A 5-year-old boy presented with a 1-year history of progressive painless abdominal distension. A CT revealed a 19 × 19 × 11 cm3 cystic mass in the right hemiabdomen, without infiltrating the surrounding structures. The tumor was completely removed by surgery. The microscopic and immunohistochemical analyses confirmed peritoneal mesothelioma. Comprehensive genomic profiling revealed no major driving mutations including BAP1, no fusions, but with amplifications of AURKA, AURKC, HLA-1B, ZNF-217, OR5F1 and MEN1 genes. Imaging follow-up 3 months after surgery revealed metastatic disease. The patient died of pneumonia at another hospital shortly after the last follow-up examination at our institution. Pediatric peritoneal mesothelioma is an extremely rare malignancy with limited targeted options and a poor prognosis. Some of the identified molecular genomic biomarkers require further exploration and validation in this cancer.

Abstract Lipofibromatosis (LF) is a rare benign fibrofatty tumor of infancy and childhood with a predilection for distal extremities, poor margination, and a high local recurrence rate. We report a toddler who presented with an LF involving her right labiocrural fold. Imaging showed a soft tissue mass extending through the right labiocrural fold with possible infiltration into the underlying muscles. The mass was excised entirely, preserving adjacent structures. The histopathologic report revealed the mass to be LF. A 3-year follow-up revealed no disease recurrence. No other cases of LF in this localization have been presented in the literature. Despite its rarity, LF should be considered in diagnosing soft tissue neoplasms in children. Accurate diagnosis and proper surgical management with complete resection are essential to reduce the postoperative recurrence risk.

Glioblastoma multiforme (GBM) is the most frequent type of primary astrocytomas. We examined the association between single nucleotide polymorphisms (SNPs) in Aurora kinase A (AURKA), Aurora kinase B (AURKB), Aurora kinase C (AURKC) and Polo-like kinase 1 (PLK1) mitotic checkpoint genes and GBM risk by qPCR genotyping. In silico analysis was performed to evaluate effects of polymorphic biological sequences on protein binding motifs. Chi-square and Fisher statistics revealed a significant difference in genotypes frequencies between GBM patients and controls for AURKB rs2289590 variant (p = 0.038). Association with decreased GBM risk was demonstrated for AURKB rs2289590 AC genotype (OR = 0.54; 95% CI = 0.33–0.88; p = 0.015). Furthermore, AURKC rs11084490 CG genotype was associated with lower GBM risk (OR = 0.57; 95% CI = 0.34–0.95; p = 0.031). Bioinformatic analysis of rs2289590 polymorphic region identified additional binding site for the Yin-Yang 1 (YY1) transcription factor in the presence of C allele. Our results indicated that rs2289590 in AURKB and rs11084490 in AURKC were associated with a reduced GBM risk. The present study was performed on a less numerous but ethnically homogeneous population. Hence, future investigations in larger and multiethnic groups are needed to strengthen these results.

The identification of mutually exclusive somatic mutations shared among myeloproliferative neoplasm (MPN) subtypes has provided a powerful tool for studying disease evolution. Clinical features, gene mutations, and survival over 18 years were analyzed in MPN patients. One hundred thirty-eight MPN patients were subcategorized according to MPN subtypes: essential thrombocythemia (ET, n = 41), polycythemia vera (PV, n = 56), primary myelofibrosis (PMF, n = 10), and MPN unclassified (MPN-U, n = 31). Patient characteristics included clinical parameters, overall survival (OS), and mutational status of the Janus kinase 2 (JAK2), calreticulin (CALR), and myeloproliferative leukemia virus oncogene (MPL) genes. We compared hematologic and clinical features of JAK2V617F-ET vs. CALR-mutated ET vs. JAK2V617F-PV patients. JAK2V617F-patients had higher values of erythrocytes, hemoglobin, and hematocrit compared to CALR-mutated patients (p < 0.05). The mutant allele burden in JAK2V617F-PV and JAK2V617F-ET patients directly correlated with erythrocyte, hemoglobin, and hematocrit values, but it inversely correlated with platelet count. Thus, mutant allele burden was an indicator of the clinical phenotype in JAK2V617F-MPN patients. OS was not affected by the mutational status. In general, mutated JAK2, CALR, and MPL genes left specific hematological signatures.

Single nucleotide polymorphisms (SNPs) in genes encoding mitotic kinases could influence development and progression of gastric cancer (GC). Case-control study of nine SNPs in mitotic genes was conducted using qPCR. The study included 116 GC patients and 203 controls. In silico analysis was performed to evaluate the effects of polymorphisms on transcription factors binding sites. The AURKA rs1047972 genotypes (CT vs. CC: OR, 1.96; 95% CI, 1.05–3.65; p = 0.033; CC + TT vs. CT: OR, 1.94; 95% CI, 1.04–3.60; p = 0.036) and rs911160 (CC vs. GG: OR, 5.56; 95% CI, 1.24–24.81; p = 0.025; GG + CG vs. CC: OR, 5.26; 95% CI, 1.19–23.22; p = 0.028), were associated with increased GC risk, whereas certain rs8173 genotypes (CG vs. CC: OR, 0.60; 95% CI, 0.36–0.99; p = 0.049; GG vs. CC: OR, 0.38; 95% CI, 0.18–0.79; p = 0.010; CC + CG vs. GG: OR, 0.49; 95% CI, 0.25–0.98; p = 0.043) were protective. Association with increased GC risk was demonstrated for AURKB rs2241909 (GG + AG vs. AA: OR, 1.61; 95% CI, 1.01–2.56; p = 0.041) and rs2289590 (AC vs. AA: OR, 2.41; 95% CI, 1.47–3.98; p = 0.001; CC vs. AA: OR, 6.77; 95% CI, 2.24–20.47; p = 0.001; AA+AC vs. CC: OR, 4.23; 95% CI, 1.44–12.40; p = 0.009). Furthermore, AURKC rs11084490 (GG + CG vs. CC: OR, 1.71; 95% CI, 1.04–2.81; p = 0.033) was associated with increased GC risk. A combined analysis of five SNPs, associated with an increased GC risk, detected polymorphism profiles where all the combinations contribute to the higher GC risk, with an OR increased 1.51-fold for the rs1047972(CT)/rs11084490(CG + GG) to 2.29-fold for the rs1047972(CT)/rs911160(CC) combinations. In silico analysis for rs911160 and rs2289590 demonstrated that different transcription factors preferentially bind to polymorphic sites, indicating that AURKA and AURKB could be regulated differently depending on the presence of particular allele. Our results revealed that AURKA (rs1047972 and rs911160), AURKB (rs2241909 and rs2289590) and AURKC (rs11084490) are associated with a higher risk of GC susceptibility. Our findings also showed that the combined effect of these SNPs may influence GC risk, thus indicating the significance of assessing multiple polymorphisms, jointly. The study was conducted on a less numerous but ethnically homogeneous Bosnian population, therefore further investigations in larger and multiethnic groups and the assessment of functional impact of the results are needed to strengthen the findings.

Introduction: Cancer of the prostate (PCa) is the second most common cancer-related cause of death among men and the most common non-cutaneous malignancy in Western countries. Numerous papers have been published on the topic of various aspects of this disease; however, rather little has been written on the diagnostic and prognostic value of the prostate cancer obtained from needle biopsy. Aim: To examine the utility of Pixel Prostate software in determining the volume and topographic distribution cancer of the prostate (PCa), and to analyze it with other variables that are characteristic for PCa. Methods: retrospectively, 75 patients data and postoperative prostate specimens were analyzed, after determining topographic distribution and cancer volume (PCa), using PixelProstate software. Results: Mean VPCa was 6.99 cm3 (0.14-29.7; median 4.51), and mean percentage cancer volume relative to prostate volume (%VPCa) was 16% (0.1-67.2%; median 13%). 71% of the patients had T2 stage, while the rest had T3 stage. Apex involvement was present in 65% of the patients, while central zone involvement and extraprostatic extension were present in 23.5% and 22.7% of the patients, respectively. Preoperative Gleason score undergrading was present in 27 (36%) patients, while bilateral PCa finding was increased from 51% to 87%, postoperatively. The most discriminant variable according to the prediction of %VPCa>10% had preoperative bilateral needle biopsy findings, with AUC of 0.75 (<.001), with sensitivity and specificity of 84% and 70%, respectively; (+LR 2,8; PPV of 74%; NPV of 82%). %VPCa showed good correlation with prostate specific antigen (PSA) and PSA-density. Conclusion: A possibility of precise spatial orientation and volume characterization of the PCa by PixelProstate software was shown. Simultaneously, with time, a clinician, experienced by PP software feedback, gets better insight for the planning of future prostate biopsy, as an important factor in clinical decision making.

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.

OBJECTIVE We present a case of relapsing tumefactive demyelination in a young female patient, that posed a real diagnostic challenge, with a heterogeneous clinical picture, atypical for multiple sclerosis (MS) presentation, and neuroradiological manifestations with a high suspicion of neoplastic diseases. CASE REPORT An 18-year old female patient presented to our Neurosurgical Out-patients' Clinic with symptoms atypical for multiple sclerosis, unremarkable neurological deficit, one tumefactive lesion on MRI, followed by relapse and another two lesions within a period of six months. We decided to perform biopsy of the tumefactive lesion with compressive effect. Serological and clinical data were negative for MS, and the patient did not respond well to corticosteroid therapy. Fresh frozen tumor tissue aroused a strong suspicion of gemistocytic astrocytoma, so total resection was done, but the definitive pathohistological examination confirmed tumefactive demyelination. CONCLUSION For clinicians, it is important to consider demyelinating disease in the differential diagnosis of a tumorlike lesion of the central nervous system, in order to avoid invasive and potentially harmful diagnostic procedures, especially in younger patients.

OBJECTIVE We present a case of relapsing tumefactive demyelination in a young female patient, that posed a real diagnostic challenge, with a heterogeneous clinical picture, atypical for multiple sclerosis (MS) presentation, and neuroradiological manifestations with a high suspicion of neoplastic diseases. CASE REPORT An 18-year old female patient presented to our Neurosurgical Out-patients' Clinic with symptoms atypical for multiple sclerosis, unremarkable neurological deficit, one tumefactive lesion on MRI, followed by relapse and another two lesions within a period of six months. We decided to perform biopsy of the tumefactive lesion with compressive effect. Serological and clinical data were negative for MS, and the patient did not respond well to corticosteroid therapy. Fresh frozen tumor tissue aroused a strong suspicion of gemistocytic astrocytoma, so total resection was done, but the definitive pathohistological examination confirmed tumefactive demyelination. CONCLUSION For clinicians, it is important to consider demyelinating disease in the differential diagnosis of a tumorlike lesion of the central nervous system, in order to avoid invasive and potentially harmful diagnostic procedures, especially in younger patients.

Glioma surgery has been the main component of glioma treatment for decades. The surgi- cal approach changed over time, making it more complex and more challenging. With molecular knowledge and diagnostic improvement, this challenge became maximally safe resection of tumor, which resulted in prolonged overall survival, progression-free period, and a better quality of life. Today, the standard glioma treatment includes maximally safe resection, if feasible, administration of temozolomide, radiotherapy, and chemotherapy. Surgical resection is performed as subtotal resection, gross total resection, and supratotal resection. Subtotal resection is the resection where a part of tumor is left. Gross total resection is a complete removal of the magnetic resonance imaging (MRI) visible tumor tissue. Supratotal resection is performed as gross total resection with excising the MRI visible tumor tissue borders into the unaffected brain tissue. Before we make final decision on which type of resection should be performed, many factors have to be considered. The question has to be answered: what the actual impact of resection on the progression of glioma is and what the functional risk of resection is.