OBJECTIVES:Evaluation of the impact of surgical treatment on malignant transformation (MT) of adult supratentorial infiltrative grade II gliomas (G2G) in a series of chemotherapy and radiotherapy-naïve patients.BACKGROUND:Despite G2G are slow-growing tumours, they typically undergo MT with a subsequent fatal disease course. An extensive resection alone likely changes their biological behaviour and defers MT; however, this impact is not unequivocally confirmed.METHODS:Thirty-eight chemotherapy and radiotherapy-naïve adult patients operated from 2005 till 2014 for a G2G were investigated. Based on postoperative magnetic resonance imaging (MRI) and/or positron emission tomography follow-up (FU) scans, the patients were classified as "transformers" (15 patients in whom MT occurred during the FU-period) and "non-transformers" (23 patients).RESULTS:The follow-up period of "non-transformers" was longer (p <0.0001). After adjustment for known risk factors - age, male sex, astrocytoma histology, preoperative tumour volume, preoperative contrast enhancement and positive isocitrate dehydrogenase 1 gene mutation status - a larger log postoperative tumour volume (p=0.031) and a smaller extent of resection (p=0.0086) were associated with a shorter MT-free survival.CONCLUSION:In our series, less extensive resections were associated with a shorter time to MT. Our data support an adoption of techniques enabling extensive G2G resections, such as intraoperative imaging and awake resections, into everyday routine (Tab. 1, Fig. 2, Ref. 40).

Objective. In recent years, the role of the modern inflammatory markers TREM-1 (triggering receptors expressed on myeloid cells) and HMGB1 (high mobility group box 1 protein) in tumorigenesis has begun to be studied. Their role in gliomas is not clear. The aim of our study was to find the role of inflammation in gliomas. Patients and Methods. In 63 adult patients with gliomas and 31 healthy controls, the expressions of TREM-1 and TREM-2 on CD14(+) blood cells (method: flow cytometry) and the levels of soluble sTREM-1, HMGB1, IL-6, and IL-10 (Elisa tests) were analyzed. Results. Cox proportional hazard analysis showed that a TREM-1/TREM-2 ratio was associated with reduced overall survival (HR=1.001,P=0.023). Patients with a TREM-1/TREM-2 ratio above 125 survived significantly shorter than patients with a TREM-1/TREM-2 ratio below 125. The percentage of CD14(+)TREM-1(+)cells was strongly associated with a plasma IL-6/IL-10 ratio (positively) and with IL-10 (negatively). Conversely, we found a higher percentage of CD14(+)TREM-2(+)monocytes in better surviving patients; these cells could downregulate the exaggerated inflammation and potentiate the phagocytosis in the tumor. The serum levels of HMGB1 negatively correlated with the percentage of CD14(+)TREM-1(+)cells and with the TREM-1/TREM-2 ratio. The positive correlation between the serum levels of a late proinflammatory cytokine HMGB1 with the percentage of TREM2(+)CD14(+)monocytes can be explained as an effort for suppression of systemic inflammation by anti-inflammatory acting CD14(+)TREM-2(+)cells. Conclusion. We showed that the TREM-1/TREM-2 ratio (expression on the surface of blood monocytes) could help predict prognosis in patients with gliomas, especially in high-grade gliomas, and that systemic inflammation has an impact on the patient's overall survival. This is the first study that showed that TREM expression on monocytes in peripheral blood could help predict prognosis in patients with gliomas.

We report on a simple iron oxide (Venofer) labeling procedure of dental pulp mesenchymal stem cells (DP-MSCs) and DP-MSCs transduced with yeast cytosinedeaminase::uracilphosphoribosyltransferase (yCD::UPRT-DP-MSCs). Venofer is a drug approved for intravenous application to treat iron deficiency anemia in patients. Venofer labeling did not affect DP-MSCs or yCD::UPRT-DP-MSCs viability and growth kinetics. Electron microscopy of labeled cells showed internalized Venofer nano particles in endosomes. MRI relativity measurement of Venofer labeled DP-MSCs in a phantom arrangement revealed that 100 cells per 0.1 ml were still detectable. DP-MSCs or yCD::UPRT-DP-MSCs and the corresponding Venofer labeled cells release exosomes into conditional medium (CM). CM from yCD::UPRT-DP-MSCs in the presence of a prodrug 5-fluorocytosine caused tumor cell death in a dose dependent manner. Iron labeled DP-MSCs or yCD::UPRT-DP-MSCs sustained their tumor tropism in vivo; intra-nasally applied cells migrated and specifically engrafted orthotopic glioblastoma xenografts in rats.

Intravascular large B-cell lymphoma (IVLBCL) is a rare variant of extranodal large B-cell lymphoma and it is characterized by selective intravascular proliferation of malignant cells. Typical features of the disease include aggressive behavior, rapid and frequently fatal course. Clinical picture is non-specific and heterogeneous, depending on the affected organ. It is not uncommon that this unique type of lymphoma is diagnosed post mortem. Herein, we report two cases of IVLBCL with neurologic symptomatology. In our clinical study patient 1 was an 80-year-old male with mixed paraparesis of lower extremities and difficulties with sphincter control. Patient 2 (56-year-old male) had vision malfunction, mental status changes and defect in phatic and motor functions. In both cases definite diagnosis was established by histological examination of necroptic material. We propose to include IVLBCL in differential diagnostic considerations in patients presenting with gradually impairing neurological status and spinal cord damage of unknown etiology (Fig. 2, Ref. 9).

Foreign substances get into the internal environment of living bodies and accumulate in various organs. Cristobalite and hematite particles in the glial cells of pons cerebri of human brain with diagnosis of Behhet disease with scanning electron microscopy (SEM), energy-dispersive microanalysis (EDX), and transmission electron microscopy (TEM) with diffraction were identified. SEM with EDX revealed the matter of irregular micrometer-sized particles sometimes forming polyhedrons with fibrilar or stratified structure. It was found in some particles Ti, Fe, and Zn. Some particles contained Cu. TEM and electron diffraction showed particles of cristobalite and hematite. The presence of the particles can be a result of environmental effect, disruption of normal metabolism, and transformation of physiologically iron-ferrihydrite into more stable form-hematite. From the size of particles can be drawn the long-term accumulation of elements in glial cells.

The impact of growth rate of supratentorial infiltrative grade II gliomas on their prognosis has been shown to be highly significant. This is probably one of the most important prognostic markers predicting a risk of early malignant transformation. The aim of this summary report is to describe current knowledge concerning the impact of growth rate of untreated grade II gliomas on their prognosis as well as to describe the options for growth rates quantification.

Breast carcinoma is the most common cancer with high mortality caused by metastatic disease. New molecular biomarkers predicting the tumour's metastatic potential would therefore improve metastasis prevention and personalised care. The aim of the study was to investigate the relationship between DNA methylation levels in invasivity and metastasising associated genes with aberrant protein expression and also to evaluate whether a similar DNA methylation level is present in the tumour and circulating cell-free DNA for utilising plasma DNA methylation as prognostic biomarker. By using pyrosequencing, we analysed DNA methylation levels of 11 genes, namely APC, ADAM23, CXCL12, ESR1, PGR B, CDH1, RASSF1A, SYK, TIMP3, BRMS1 and SOCS1 in tumour, plasma and peripheral blood cells from 34 patients with primary breast cancer, as well as plasma and peripheral blood cells from 50 healthy controls. Simultaneously, the expression of related proteins in paraffin-embedded tumour samples was evaluated by immunohistochemistry. Statistical analysis was performed by SPSS statistics 15.0 software. Tumour DNA hypermethylation was found in most commonly methylated RASSF1A (71.9%), APC (55.9%), ADAM23 (38%) and CXCL12 (34.4%) genes with methylation levels up to 86, 86, 53 and 64 %, respectively. In tumours, significantly higher methylation levels were found in nine genes, compared with the patients´ peripheral blood cell DNA. Furthermore, in patients methylation levels in peripheral blood cell DNA were significantly higher than in controls in CXCL12, ESR1 and TIMP3 genes, but the values did not exceed 15%. On the other hand, no correlations were observed in patients between DNA methylation in tumours and cell-free plasma DNA. Moreover, in patients and controls nearly identical values of cumulative DNA methylation (43.6 % ± 20.1 vs. 43.7 % ± 15.0) were observed in plasma samples. A variable spectrum from high to none expressions presented in tumour tissues in all of the proteins evaluated, however in APC and CXCL12 genes a visible decreasing trend of mean DNA methylation level with increasing expression of the corresponding protein was observed. The DNA methylation profiles manifested in our group of breast carcinomas are cancer specific, but they are not the only cause that affects the silencing of evaluated genes and the decrease of relevant protein products. The clinical utility of DNA methylation testing in peripheral blood cell DNA for cancer diagnosis and therapy need to be further investigated.

BACKGROUND:Primary intracranial germ cell tumors represent a rare category of neoplasms, which occur in children and young adults. The WHO classification divides intracranial tumors into germinomas and non-germinomas. The most frequent locality of these tumors is pineal and suprasellar region. Clinical signs and symptoms depend on the localization of the tumour - they most commonly include signs of increased intracranial pressure, Parinauds syndrome, bitemporal hemianopsy and signs of endocrine deficiency. Gadolinium enhanced MRI scan of the brain is the imagining examination of choice in the diagnostic strategy of intracranial germ cell tumors. However, the imagining studies do not provide sufficient information about histological type; therefore, biopsy is necessary. The exception represents cases with characteristically increased levels of tumor markers (AFP and β-HCG) measured in the serum and cere-brospinal fluid.CASE:A pineal germ cell tumor was observed in a 26-year-old male with presentation of an eye-sight disorder with focusing difficulty and photophobia, accompanied by intensive fatigue and sleepiness, nausea with occasional vomiting, intermittent headaches and Parinauds syndrome. MRI examination of the brain showed tumor expansion in the pineal region and in the right part of the mesencephalon. Radical extirpation of the tumor in the pineal region was performed. The follow-up MRI scan of the brain revealed relapse of the disease. The patient underwent craniospinal radiation therapy with subsequent postoperative chemotherapy (regimen cisplatin and etoposide), three cycles in total. Currently, the patient is 30 months after finishing of oncological treatment in clinical remission of the disease.CONCLUSION:The treatment and prognosis of this neoplasm differ between particular categories. Germinomas have better survival rates than non-germinomas. A 5-year survival rate of germinoma patients after application of radiotherapy alone was > 90% of cases. The addition of chemotherapy lead to a decrease of the dose and minimalization of the irradiated area, with achievement of fewer side effects without a decrease of the curability. Non-germinomas are less radiosensitive than germinomas, but after the application of the adjuvant chemotherapy, survival benefit was achieved. However, the optimal management of these tumors remains controversial.

OBJECTIVE To analyze the immune status in situ of tonsils of patients with recurrent tonsillitis (RT) and idiopathic tonsillar hypertrophy (ITH) with the aim to discuss the indications of tonsillectomy (TE) and tonsillotomy (TT) in young children. METHODS The histological and immunohistological study of tonsillar tissue of RT and ITH in correlation with immunological parameters in peripheral blood in 13 patients with RT and 16 patients with ITH. RESULTS In the RT group, we found a higher degree of fibrosis with a higher density of memory lymphocytes (CD45R0+), B-lymphocytes (CD20+) and cytotoxic T-lymphocytes (CD8+) in surface epithelium of tonsils compared to the ITH group (NS). The density of immunoglobulin IgG in the crypt epithelium in RT was significantly higher than in the ITH group (p = 0.041). We also measured a higher sera concentration of immunoglobulines (IgG, IgM, IgA) and TNF-α in RT compared to the ITH group (NS) and TH-1 immune response in tonsillar tissue based on differences between local cytokine concentration TNF-α and IL-4. CONCLUSIONS RT has a higher inflammatory reaction in tonsillar tissue as a result of persistent bacterial antigenic stimulation. In patients with RT, the tonsillectomy might be the only option for surgical treatment. In patients with ITH with mild symptoms, the tonsillotomy should be preferred (Tab. 3, Ref. 24).

UNLABELLED:Gliosarcoma (GS) is a relatively rare glioblastoma variant characterized by biphasic glial and mesenchymal differentiation patterns. The sarcomatous part most commonly resembles fibrosarcoma or so-called malignant fibrous histiocytoma. Rarely, GS shows heterologous lines of differentiation in the form of osteosarcoma, chondrosarcoma, liposarcoma, leiomyosarcoma, squamous or glandular malignant epithelial differentiation, or primitive neuroectodermal tumor (PNET)-like foci. When rhabdomyoblastic differentiation occurs, it is in the form of malignant spindle cells, with cross-striated strap cells or rounded rhabdomyoblasts reminiscent of the embryonal type of rhabdomyosarcoma. We are reporting a case of GS with an alveolar rhabdomyosarcoma-like component. The tumor consisted of poorly differentiated primitive small round cells growing in a solid and alveolar pattern, with minimal cytoplasm, markedly elevated mitotic activity and numerous apoptotic nuclei. Rhabdomyosarcomatous differentiation was confirmed by desmin and myogenin immunopositivity. To the best of our knowledge, this histologic pattern has not been previously reported in GS. Differential diagnostic considerations are discussed.KEYWORDS:gliosarcoma - alveolar rhabdomyosarcoma - myogenin - desmin.

We report on a case of urinary bladder leiomyosarcoma in a 23-year-old woman, 22 years after therapy for bilateral retinoblastoma. The tumor presented with dysuria and macroscopic haematuria. Cystoscopy revealed a tumor localized in the trigonum covered by an ulcerated urothelium. The patient underwent a transvesical tumor resection. Eight months later, a second leiomyosarcoma developed in the vertex, at a site different from the previous one. A cystoscopic trans-urethral tumor resection was performed, followed by combined chemotherapy. One year later another recurrence occurred at the site of the primary resection. Open laparotomic resection of the involved bladder wall was performed. The patient remains both recurrence and metastases free after twenty months of follow-up. Molecular analysis of the peripheral blood showed rare germline point mutation in the intron 24 of the RB1 gene. FISH analysis of the tumor tissue revealed polyploid cells with relative loss of normal RB1 gene locus, indicating deletion and second hit loss of the second RB1 allele function. Along with the ten previously reported cases, this report suggests a non-random association between the hereditary retinoblastoma and urinary bladder leiomyosarcoma. Therapy with cyclophosphamide seems to be an important risk factor. Life-long surveillance for second malignancies, including bladder leiomyosarcoma is therefore mandatory in these patients.

Objective: Detection of anaplastic areas within focally malignant infiltrative brain glioma is an important diagnostic step in preventing histopathological undergrading. The objective of this paper is to draw attention to the possibility of intraoperative detection of anaplastic foci within infiltrative gliomas using 5-aminolevulic acid (5-ALA). Material and methodology: We prospectively studied a case series of five adult patients harboring infiltrative supratentorial gliomas with nonsignificant contrast enhancement (CE) on preoperative magnetic resonance imaging. The patients were operated on during a period of 10 months. All patients were administered 5-ALA before the surgery. After illuminating the operative field with violet-blue light (wavelength 400 nanometers), selective tissue samples were taken from fluorescing and non-fluorescing areas. Histopathological diagnosis was established according to World Health Organization (WHO) 2007 diagnostic consensus criteria. Cell proliferation was assessed immunohistochemically by Ki-67 labeling index (LI). Results: Focal 5-ALA fluorescence was observed within four gliomas. All tissue samples taken selectively from fluorescing parts of these tumors were histopathologically evaluated as WHO grade III. The average Ki-67 LI in fluorescing parts was 14.13%. In contrast, all tissue samples taken selectively from nonfluorescing parts of these tumors corresponded to WHO grade II. Average Ki-67 LI in nonflourescing parts was 2.67%. In one glioma, no intraoperative 5-ALA fluorescence was observed; all tissue samples sent to histopathological examination were proven to be WHO grade II, the average Ki-67 LI was 3%. Conclusions: Using 5-ALA may be a useful method in detecting anaplastic foci within infiltrative gliomas with nonsignificant CE.

Classification, grading and treatment of central nervous system tumors is currently based on morphology. Advances in molecular biology help to clarify pathogenesis, refine prognosis and detect potential targets for targeted therapy in a wide spectrum of CNS tumors. In this short review we present our view on selected diagnostic, prognostic and predictive biomarkers of primary CNS tumors, with an emphasis on application in daily praxis.

Advanced malignant melanoma is incurable by the current means of therapy. Traditional morphological classification (nodular melanoma, lentigo maligna melanoma, nevoid melanoma etc.) does not have any significant prognostic or predictive impact. Recent advances in molecular pathogenesis and the availability of targeted therapies have produced several positive results. In the near future, the main challenge for pathologists, geneticists and oncologists will be the identification of accurate therapeutic targets, as well as mechanisms of resistance, in melanoma in the particular patient in care.

BACKGROUNDCentral neurocytoma is a rare primary brain tumour, mostly localised in the lateral ventricles in relation to the foramen of Monro.OBJECTIVESTo report a case of a rare central neurocytoma with a complete loss of Synaptophysin expression and provide the differential diagnosis.METHODS AND RESULTSWe describe a case of a 34-year old man with a headache, unsteady gait and dim vision. MRI demonstrated a tumorous expansion localised in both lateral ventricles. The patient underwent a subtotal resection. Histology showed a picture consistent with central neurocytoma, but tumour was completely negative for Synaptophysin. We describe our approach in such a diagnostically difficult case.CONCLUSIONSIn the rare case of Synaptophysin-negative central neurocytoma, its neuronal differentiation should be substantiated by electron-microscopic examination. Unfortunately in the routine work, biopsy samples are usually fixed in formalin fixative which does not preserve ultrastructure well. In such situations, an accurate diagnosis is disputable and based on careful assessment of the histological features, exclusion of tumours with similar morphology and detailed correlation with MRI pictures (Fig. 4, Ref. 6). Full Text (Free, PDF) www.bmj.sk.

We report a case of post-radiation dedifferentiation of meningothelial meningioma into chondroblastic osteosarcoma. The tumor developed in a 61-year-old man, seven years after adjuvant stereotactical radiotherapy of recurring meningioma. Histologically, there was a continuous transition from atypical meningioma into chondroblastic osteosarcoma. The patient died three weeks after the surgery, without additional oncological treatment. To our knowledge, this case represents only the second reported case of post-radiation dedifferentiation of meningioma into osteosarcoma.