Malignant melanoma of the nasal mucosa

Nose's Paranasal sinus & malignant melanoma are rarely seen, bold tumor with a prevalence rates of 0.68 percent across every malignant tumor. The neuroectodermal cells which are termed as Melanomas are found in skin's base layer, iris’s vascular intraocular coat, skin adnexa, & infrequently into outer covering of mucous. Blockage feeling of nose & bleeding from the nose are the symptoms which are most commonly reported, however patient may have symptoms that are nonspecific, leading to a delay in diagnosis which results in appropriate prediction of treatment's outcome. This study defines a 70 years female with the history of nose blockage feeling. Physicians suggest performing Nose’s CT scan, in which they came to know that large polypoidal portion in right nostril, extending to the nasopharynx, and eroded part of the sinus wall, septum and right medial pterygoid plate. Immunochemical study done revealed positive results for S100, vimentin, & HMB-45, which made the outcome suitable for tumor. An individual suffering from this will have no recurrence.

The importance of serum immunoglobulin free light chain assessment for predicting outcome in patients with newly diagnosed multiple myeloma in real clinical practice

Background. The prognosis of patients with multiple myeloma (MM) is significantly different depending on the biological characteristics of the tumor substrate, the microenvironment of the bone marrow, as well as factors associated with the patient’s body. Therefore, the search for new reliable and easily identifiable prognostic markers is relevant for the effective management of patients with this disease.The objective of the study was to assess the prognostic value of the study of serum free light chains (FLC) of immunoglobulins κ and λ and their ratio κ / λ FLC in the blood serum of patients with newly diagnosed MM in real clinical practice.Materials and methods. 369 patients with first diagnosed MM (134 men and 235 women) were examined who were hospitalized in the hematology department of the City Clinical Hospital No. 2 Novosibirsk in the period since January 2012 to December 2017. The median age of the patients was 67 (32–82) years. All patients received induction courses of chemotherapy based on bortezomib. The control group consisted of 56 conditionally healthy individuals: 34 women (60.7 %) and 22 (39.3 %) men with a median age of 62 (40–68) years. The concentration of FLC-κ and FLC-λ (mg / L) in blood serum was determined by immunoturbidimetric method on a Hitachi 911 automated biochemical analyzer using the Freelite Human Lambda and Freelite Human Kappa reagent kits (Binding Site, Great Britain).Results. It was found that in patients with MM, the concentration of serum FLC-κ or FLC-λ was statistically significantly higher compared to the control group and varied depending on the type of MM (p <0.001). The diagnostic sensitivity of the quantitative determination of FLC and their ratio for MM was 98.64 %, compared with 94.04 % in a standard immunochemical study. The values of the ratio κ / λ FLC <0.04 or> 65, as well as the concentration of FLC-κ and FLC-λ are higher than the median obtained in the whole group (FLC-κ ≥702 mg / L and FLC-λ ≥493.2 mg / L), correlate with known factors of poor prognosis for MM (with a high concentration of β2‑microglobulin (>3.5 mg / L) (r = 0.461; p <0.001), plasma cell bone marrow infiltration >60 % (r = 0.420; p <0.001), renal failure (creatinine >177 μmol / L) (r = 0.380; p = 0.002), and also with high lactate dehydrogenase activity (>450 U / L) (r = 0.520; p <0.001) and is associated with poor outcomes. The median overall survival in the group of patients with κ / λ FLC <0.04 or >65 was 49 months compared to 76 months in the group with κ / λ FLC 0.04–65 (log-rank p = 0.012).Conclusion. The determination of free FLC in the blood serum of patients with MM can be used to assess the prognosis of their survival. The value of the κ / λ FLC ratio <0.04 or >65 allows us to divide patients with MM into risk groups with significantly different outcomes and can be used to identify patients at high risk who need more aggressive therapy and more detailed monitoring of the response.

AB0518 CRYOGLOBULINEMIC VASCULITIS ASSOCIATED WITH HCV INFECTION AND PRIMARY SJOEGREN’S SYNDROME: DATA FROM A SINGLE CENTER EXPERIENCE

Background:According to some publications [1] cryoglobulinemic vasculitis in different associated diseases varies.Objectives:To characterize patients with cryoglobulinemic vasculitis (CV) in primary Sjoegren’s syndrome (pSS) and chronic hepatitis C virus (HCV) infectionMethods:54 patients with CV were recruited to this study during 7 years period in our rheumatological center. CV was diagnosed according criteria proposed by Ferri C. [1] and De Vita [2].22 patients had CV associated with HCV (19 women and 3 men) and 32 with pSS (all female). The mean age of patients at the time of inclusion in the study among HCV and pSS patients was 50.4±10.0 years and 55.8±13.5 years, and at CV onset was 42.8± 11.1 years and 47.1±15.3 years (p>0,05).Results:19 patients (86%) with HCV-CV had viremia with prevailed 1b genotype (84%). 8 (42%) patients had severe liver fibrosis (F3-4). SS was diagnosed in 6 (28%) patients with HCV-CV (3 with sSS and 3 with pSS). An increase of aRo antibodies (>50 U / ml) was detected in 3patients, ANA>1/320 - in 5/6 patients. 2 patients with SS were diagnosed MALT-lymphoma of the enlarged salivary and lacrimal glands, and 1 marginal zone lymphoma of the spleen in a patient with HCV-CV without pSS. All patients with lymphoma had type II cryoglobulinemia.Most patients with pSS -CV had late stage and active disease: xerostomia (<0.5 ml/5 min) in 28 (88%), sialoadenitis (>2 foci in MSG), keratoconjunctivitis sicca (in 22 patients, 69%).Lymphomas were diagnosed in 9 patients with pSS-CV (28%). In all cases, they were non-Hodgkin’s lymphomas (NHL): in 7 patients - MALT lymphomas of enlarged parotid salivary (5), lacrimal glands (2), in 5 cases they were accompanied by regional lymph node enlargement. B-cell marginal zone lymphoma of lymph nodes and B-cell large cell lymphoma were observed in 1 case each.No statistically significant differences were found in 2 groups in clinical manifestations of CV (see Graph.1), although patients with pSS had elevated lymphoma rate (28% compared to 6% for HCV, p=0.08), while in HCV-CV a slightly higher incidence of arthritis (22%, p=0.14), glomerulonephritis (56% vs 31% in pSS, p=0.10), and enanthema (19% and 3%, respectively, p=0.06).Type II cryoglobulinemia was detected in 68% cases of HCV-CV and in 72% with pSS, less often mixed polyclonal (27% vs 22%) and oligoclonal (5% and 6%) types. There was in 96% (44/46) cases monoclonal IgM with predominant K-light chain mIg (87%, n=40/46).RF positivity, low C4 complement, increased CRP and the levels of IgG, IgM in 2 groups were almost the same. Obviously pSS-CV group had significantly increased aRo, aLa, ANF titers (p=0.01) and also elevated IgA (p=0.02), lowered CD19+ cell levels (p=0.008) and increased BAFF (p=0.04), while in HCV-CV group high transaminases were typical (p=0.0008). BAFF level (N<0.8 ng/ml) in pSS-CV group was higher (median 2.73 ng / ml (0.66-3.86) than in HCV (median 0.66 ng / ml (0.14 - 0.92), (p=0.04). Patients with pSS-CV had significantly (p=0.008) lowered CD19 + cell count (median 5.3% (2.2-13.6)) if the normal range was 6-19%, in contrast to patients with HCV-associated CV (median 20.5% (13.2-26.0).Graphic 1. Clinical characteristics of HCV and pSS associated CVGraphic 2. Laboratory characteristics of HCV and pSS associated CVConclusion:Clinical picture of CV, as well as the main immunological parameters are similar in patients with associated pSS and HCV. Immunochemical study of serum and urine proteins is required to determine the type of cryoglobulinemia. SS is not rare in HCV-CV, so appropriate examination with ANA, aRo/La detection is mandatory. Patients with mixed monoclonal cryoglobulinemia had increased risk of hematological malignancies.References:[1]Ferri C, Zignego AL, Pileri SA. Cryoglobulins. J Clin Pathol 2002;55:4–13.[2]De Vita S, Soldano F, Isola M, et alPreliminary classification criteria for the cryoglobulinaemic vasculitisAnnals of the Rheumatic Diseases 2011;70:1183-1190.Disclosure of Interests:None declared

Serine threonine kinase 11/liver kinase B1 mutation in sporadic scirrhous-type gastric cancer cells

Scirrhous-type gastric carcinoma (SGC), which is characterized by the rapid proliferation of cancer cells accompanied by extensive fibrosis, shows extremely poor survival. A reason for the poor prognosis of SGC is that the driver gene responsible for SGC has not been identified. To identify the characteristic driver gene of SGC, we examined the genomic landscape of six human SGC cell lines of OCUM-1, OCUM-2M, OCUM-8, OCUM-9, OCUM-12 and OCUM-14, using multiplex gene panel testing by next-generation sequencing. In this study, the non-synonymous mutations of serine threonine kinase 11/liver kinase B1 (STK11/LKB1) gene were detected in OCUM-12, OCUM-2M and OCUM-14 among the six SGC cell lines. Capillary sequencing analysis confirmed the non-sense or missense mutation of STK11/LKB1 in the three cell lines. Western blot analysis showed that LKB1 expression was decreased in OCUM-12 cells and OCUM-14 cells harboring STK11/LKB1 mutation. The mammalian target of rapamycin (mTOR) inhibitor significantly inhibited the proliferation of OCUM-12 and OCUM-14 cells. The correlations between STK11/LKB1 expression and clinicopathologic features of gastric cancer were examined using 708 primary gastric carcinomas by immunochemical study. The low STK11/LKB1 expression group was significantly associated with SGC, high invasion depth and frequent nodal involvement, in compared with the high STK11/LKB1 expression group. Collectively, our study demonstrated that STK11/LKB1 mutation might be responsible for the progression of SGC, and suggested that mTOR signaling by STK11/LKB1 mutation might be one of therapeutic targets for patients with SGC.

Resveratrol Regulates BDNF, trkB, PSA-NCAM, and Arc Expression in the Rat Cerebral Cortex after Bilateral Common Carotid Artery Occlusion and Reperfusion

The polyphenol resveratrol (RVT) may drive protective mechanisms of cerebral homeostasis during the hypoperfusion/reperfusion triggered by the transient bilateral common carotid artery occlusion followed by reperfusion (BCCAO/R). This immunochemical study investigates if a single dose of RVT modulates the plasticity-related markers brain-derived neurotrophic factor (BDNF), the tyrosine kinase trkB receptor, Polysialylated-Neural Cell Adhesion Molecule (PSA-NCAM), and Activity-regulated cytoskeleton-associated (Arc) protein in the brain cortex after BCCAO/R. Frontal and temporal-occipital cortical regions were examined in male Wistar rats randomly subdivided in two groups, sham-operated and submitted to BCCAO/R. Six hours prior to surgery, half the rats were gavage fed a dose of RVT (180 mg·kg−1 in 300 µL of sunflower oil as the vehicle), while the second half was given the vehicle alone. In the frontal cortex of BCCAO/R vehicle-treated rats, BDNF and PSA-NCAM decreased, while trkB increased. RVT pre-treatment elicited an increment of all examined markers in both sham- and BCCAO/R rats. No variations occurred in the temporal-occipital cortex. The results highlight a role for RVT in modulating neuronal plasticity through the BDNF-trkB system and upregulation of PSA-NCAM and Arc, which may provide both trophic and structural local support in the dynamic changes occurring during the BCCAO/R, and further suggest that dietary supplements such as RVT are effective in preserving the tissue potential to engage plasticity-related events and control the functional response to the hypoperfusion/reperfusion challenge.

Localisation of basic fibroblast growth factor in cholesteatoma matrix: an immunochemical study

ObjectiveTo investigate the expression of basic fibroblast growth factor in the matrix of human acquired cholesteatoma compared to the deep meatal skin. This topic does not appear to have been fully investigated before.MethodsAn immunochemical study was conducted. Cholesteatoma tissues from adult patients were collected during surgery (n = 19). Control specimens were taken from the deep meatal skin (n = 8) and compared.ResultsA highly significant difference in basic fibroblast growth factor expression was identified between cholesteatoma and skin (mean ± standard error = 58.53 ± 3.6 per cent in cholesteatoma vs 40.6 ± 3.5 per cent in skin; p = 0.005). Both basal and parabasal keratinocytes were stained positive with basic fibroblast growth factor. Additionally, there was specific staining in the basal columnar middle-ear epithelium and mast cell membrane.ConclusionBasic fibroblast growth factor plays an active role in proliferative activity of cholesteatoma through its overexpression in basal and parabasal layers of cholesteatoma matrix. Moreover, its expression in the mast cell membrane supports its role in bone resorption activity.

METHYL-CpG-BINDING PROTEIN 2 IS LOCALIZED IN THE POSTSYNAPTIC COMPARTMENT: AN IMMUNOCHEMICAL STUDY OF SUBCELLULAR FRACTIONS

Rett syndrome (RS) is a developmental neurologic disordercharacterized by severe cognitive impairment, autisticbehavior, stereotypic movements, and frequently also seizures(Naidu, 1997). The disorder is associated in a majorityof cases with mutations of the coding region of thegene for methyl-CpG-binding protein 2 (MeCP2) (Shahbazianand Zoghbi, 2001; Hoffbuhr et al., 2001). More recently,other neurologic syndromes different from RS havebeen reported as associated with MeCP2 mutations (Imessaoudeneet al., 2001; Watson et al., 2001; Dotti et al.,2002). Only limited data are available about the expressionof MeCP2 in the CNS. These immunochemical studiesdescribe a predominant neuronal compartmentalization(LaSalle et al., 2001; Shahbazian et al., 2002), and apattern of expression that parallels neuronal differentiation(Akbarian et al., 2001; Shahbazian et al., 2002). Despitethis information, and considering that MeCP2 has widetissue distribution (LaSalle et al., 2001; Shahbazian et al.,2002), it is still unclear why abnormal MeCP2 expression ismainly associated with neurologic dysfunction. Moreover,recent data show that several transcription factors, withexpression in the CNS and other organs, may have aunique neuronal distribution characterized by both nuclearand synaptic localizations (Paratcha et al., 2000; Eberwineet al., 2001). For these reasons, we examined MeCP2expression in normal human neocortex with special emphasison its subcellular localization.