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.

Uvod: Heterogena priroda akutne mijeloične leukemije (AML) iziskuje primjenu specifičnih i pouzdanih laboratorijskih testova pri postavljanju dijagnoze. Istraživanja ukazuju na određene nedostatke konvencionalnih morfoloških i imunofenotipskih metoda, ali i potrebu za imple-mentacijom kompleksnog dijagnostičkog algoritma koji uz navedene metode inkorporira citogenetičke i molekularno-genetičke analize u integrirani dijagnostički pristup. Cilj: Predstaviti prednosti i nedostatke integriranog dijagnostičkog pristupa u dijagnostici akutne mijeloične leukemije. Metode: Za potrebe neeksperimentalnog kvalitativnog istraživanja, pretražene su relevantne baze podataka (PubMed, Scopus i Web of Science). Pretraga baza u širem opsegu provedena je uz pomoć ključnih riječi acute myeloid leukemia, cytomorphology, flow cytometry, cytogenetic abnormalities i molecular diagnostics. Za konačnu analizu, odabrani su naučni radovi koji zadovoljavaju kriterije relevantnosti i povezanosti s postavljenim ciljem i temom istraživanja. Rezultati: Integracija dijagnostičkih modaliteta u AML predstavlja veliki izazov zbog kontinuriane složenosti i opterećenja za zdravstvene profesionalce. Kao značajne prednosti izdvajaju se mogućnost umrežavanja rezultata različitih dijagnostičkih modaliteta, te detekcija nespecifičnih i izazovnih slučajeva AML. Prijavljeni nedostaci se odnose na potrebu za jedinstvenim protokolima, nepredvidiv turnaround time, validaciju i potrebu za visoko specija-liziranim osobljem. Danas se sve više pažnje pridaje AI (engl. artifical intelligence) i njenoj sposobnosti da obradi podatke s ciljem pružanja brzih i preciznih dijagnostičkih i prognostičkih informacija što predstavlja obećavajući koncept u AML-u. Usvajanje ove paradigme znatno bi olakšalo trenutne pristupe i unaprijedilo koncept zdravstvene zaštite. Zaključak: Integrirani dijagnostički pristup ima za cilj poboljšati kvalitet pojedinačnih metoda primjenom dosadašnjih saznanja i paralelnim testiranjem novih mogućnosti. S razvojem precizne medicine, ovaj dijagnostički model će u budućnosti dobiti dodatni značaj. Neovisno od utvrđenih prednosti i nedostatka, dostupna istraživanja ukazuju na nužnost dodatnih napora i primjenu AI za uspostavljanje standardiziranog integriranog pristupa na globalnom nivou.

Melanomacrophages of fish are commonly explored as biomarkers of water pollution and are considered to be sensitive albeit non-specific health indicators in water ecosystems. Sharks as long living marine species are good sentinel species. This study presents morphometric data for splenic and hepatic melanomacrophages (MMC), and observed histopathology in ten lesser-spotted catsharks, Scyliorhinus canicula (L.), one of the most abundant shark species in the eastern Adriatic Sea. At necropsy, we collected random tissue samples from liver, brain, gallblader, pancreas, spleen, kidney, gills, entire digestive system, thyroid gland, rectal gland, entire urogenital (male samples) and genital system (female samples). Collected tissue samples were routinely processed and stained with hematoxylin-eosin, Periodic Acid-Schiff, and Masson Trichrome for microscopic examinations and morphometry. There was a minimal number of histopathological lesions in the examined sharks, but morphometric values reported herein were three folds higher than in previous studies in free-ranging sharks. Studies on larger numbers of sharks are needed to elucidate the biological significance of our finding in the context of population decline of the lesser-spotted catshark.

Context Neoangiogenesis and lymphangio-genesis are essential for the growth of tumor and progression of malignancy. Objective The study examined the significance of VEGF-C expression in comparison to classical prognostic factors in differentiated thyroid carcinoma (DTC), as well as an independent prognostic marker in DTC. Design The study included 81 patients with DTC allocated in two groups according to the type of cancer (follicular versus papillary) and then compared to expression of VEGF-C and clinicopathological features. Methods Expression of VEGF-C was identified with anti-VEGF-C antibody using tris-EDTA buffer Antigen Retrieval Protocol. Each specimen was scored with a semi-quantitative score system (H-score). Results The analysis of T staging system showed a linear correlation between the size of a tumor, expression of VEGF-C and recurrence of a disease, with a statistical significance (p < 0.0001). There was a clear and significant correlation between VEGF-C expression and T stage in patients with papillary carcinoma (p = 0.0294). Analysis of invasion of a surgical margin demonstrated significant positivity in patients with papillary thyroid cancers who expressed VEGF-C (p = 0.0207) indicating the worse prognosis of a disease. Also a statistically significant correlation was between VEGF-C and extrathyroid extension, indicating the worse prognosis (p = 0.0133) in papillary cancers. The level of VEGF-C expression was statistically significant in patients with papillary thyroid cancer (p = 0.039). Conclusions This study undoubtedly demonstrates that VEGF-C expression is an evident negative prognostic factor in patients with papillary thyroid carcinoma, along with the classic prognostic factors, such as a larger tumor size, tumor margin involvement, extrathyroid extension, i.e. local aggressiveness.

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.

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.