Comparison of the specimen quality of endobronchial ultrasound-guided intranodal forceps biopsy using standard-sized forceps versus mini forceps for lung cancer: A prospective study.

BACKGROUND AND OBJECTIVE: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a diagnostic procedure with adequate performance; however, its ability to provide specimens of sufficient quality and quantity for treatment decision-making in advanced-stage lung cancer may be limited, primarily due to blood contamination. The use of a 0.96-mm miniforceps biopsy (MFB) permits true histological sampling, but the resulting small specimens are unsuitable for the intended applications. Therefore, we introduced a 1.9-mm standard-sized forceps biopsy (SFB) and compared its utility to that of MFB. METHODS: We prospectively enrolled patients from three institutions who presented with hilar/mediastinal lymphadenopathy and suspected advanced-stage lung cancer, or those who were already diagnosed but required additional tissue specimens for biomarker analysis. Each patient underwent MFB followed by SFB three or four times through the tract created by TBNA using a 22-gauge needle on the same lymph node (LN). Two pathologists assessed the quality and size of each specimen using a virtual slide system, and diagnostic performance was compared between the MFB and SFB groups. RESULTS: Among the 60 enrolled patients, 70.0% were diagnosed with adenocarcinoma. The most frequently targeted sites were the lower paratracheal LNs, followed by the interlobar LNs. The diagnostic yields of TBNA, MFB and SFB were 91.7%, 93.3% and 96.7%, respectively. The sampling rate of high-quality specimens was significantly higher in the SFB group. Moreover, the mean specimen size for SFB was three times larger than for MFB. CONCLUSION: SFB is useful for obtaining sufficient qualitative and quantitative specimens.

Assessing liver stiffness with conventional cut-off values overestimates liver fibrosis staging in patients who received the Fontan procedure.

AIM: Patients who undergo the Fontan procedure for complex congenital heart disease are prone to liver cirrhosis. Liver stiffness (LS) reflects liver fibrosis stage in patients with chronic viral hepatitis; however, its accuracy in predicting liver fibrosis stage in Fontan patients is controversial. We aimed to clarify the correlation between LS and liver fibrosis stage in Fontan patients. METHODS: Fifty-eight Fontan patients were prospectively measured for LS with transient elastography. We undertook liver biopsy, cardiac catheterization, and laboratory tests in 22 of these patients (median age, 14.7 years; range, 9.9-32.1 years) with LS > 11.0 kPa (median, 19.2 kPa; range, 12.2-39.8 kPa); these elevated LS values suggest liver cirrhosis. RESULTS: Histologically, all patients showed mild-to-severe portal and sinusoidal fibrosis but no cirrhosis. Statistically, LS did not predict histological liver fibrosis scores (p = 0.175). Liver stiffness was not correlated with central venous pressure (p = 0.456) or with the hepatic venous pressure gradient (HVPG; p = 0.062), although the p value for HVPG was only slightly above the threshold for significance. CONCLUSIONS: Fontan patients are prone to developing both portal and sinusoidal fibrosis. Liver stiffness could be influenced by HVPG, and using the conventional cut-off values for LS overestimates and overtreats liver fibrosis in these patients.

Giant cell tumor of bone - Analysis of 213 cases involving extra-craniofacial bones.

We elucidated clinicopathological characteristics of giant cell tumor of bone (GCTB) in Japan, and significant clinicopathological factors for predicting local recurrence. Clinicopathological profiles of 213 patients with GCTB (100 male, 113 female) involving extra-craniofacial bones were retrieved. Pathological slides obtained at the initial surgery were reviewed. Fourteen pathological and five clinical features were statistically analyzed to disclose prognostic significance. Patient age ranged from 12-80 years (Average 38.7). Long bones were most frequently affected (86.4%), especially around the knee (62.9%). Histological features are basically similar to those previously reported. Within a follow-up period (24-316 months, average 106.1 months), the local recurrence rate is 29.1%. Metastasis has occurred in 9 patients. Cox regression analysis of representative clinicopathological features shows that younger age, higher mitotic count, smaller zones of stromal hemorrhage, considerable vascular invasion and absence of ischemic necrosis are significant predictors for local recurrence. Initial operative method (curettage) is a significant risk factor in univariate analysis but not by multivariate analysis (P = 0.053). Denosumab administration increases risk but not significantly (P = 0.053). Histone 3.3 G34W immunopositivity is not significant for predicting local recurrence.

Accumulation of 8-hydroxydeoxyguanosine, L-arginine and Glucose Metabolites by Liver Tumor Cells Are the Important Characteristic Features of Metabolic Syndrome and Non-Alcoholic Steatohepatitis-Associated Hepatocarcinogenesis.

To uncover mechanisms and explore novel biomarkers of obesity, type 2 diabetes (T2DM) and nonalcoholic steatohepatitis (NASH)-associated hepatocarcinogenesis, cellular and molecular alterations in the liver, and hepatocellular carcinomas (HCCs) were investigated in NASH model 60-week-old Tsumura, Suzuki, Obese Diabetic (TSOD) mice and NASH HCC patients. Markedly elevated lipid deposition, inflammation, fibrosis, and peroxisome proliferation in the liver, preneoplastic lesions, and HCCs of TSOD mice were accompanied by accumulation of polysaccharides in the cellular cytoplasm and nuclei and increase of oxidative DNA damage marker, 8-hydroxydeoxyguanosine (8-OHdG) formation in the liver and altered foci. Metabolomics of TSOD mice HCCs demonstrated significant elevation of the concentration of amino acid L-arginine, phosphocreatine, S-adenosylmethionine/S-adenosylhomocysteine ratio, adenylate, and guanylate energy charges in coordination with tremendous rise of glucose metabolites, mostly fructose 1,6-diphosphate. L-arginine accumulation in HCCs was associated with significant under-expression of arginase 1 (ARG1), suppression of the urea cycle, methionine and putrescine degradation pathways, activation of Ser and Thr kinase Akt AKT, phosphoinositide 3-kinase (PI3K), extracellular signal-regulated kinase 1/2 (ERK1/2) kinases, ß-catenin, mammalian target of rapamycin (mTOR), and cell proliferation. Furthermore, clinicopathological analysis in 20 metabolic syndrome/NASH and 80 HCV-positive HCC patients demonstrated significant correlation of negative ARG1 expression with poor tumor differentiation, higher pathological stage, and significant decrease of survival in metabolic syndrome/NASH-associated HCC patients, thus indicating that ARG1 could become a potential marker for NASH HCC. From these results, formation of oxidative stress and 8-OHdG in the DNA and elevation of glucose metabolites and L-arginine due to ARG1 suppression in mice liver cells are the important characteristics of T2DM/NASH-associated hepatocarcinogenesis, which may take part in activating oxidative stress resistance, synthesis of phosphocreatine, cell signaling, methylation, and proliferation.

Optimal Biopsy Protocol to Evaluate Histological Effectiveness of Proton Pump Inhibitor Therapy in Patients with Eosinophilic Esophagitis.

OBJECTIVE: Recent guidelines propose that both proton pump inhibitor (PPI) responders and nonresponders are included in eosinophilic esophagitis (EoE). Although multiple biopsies should be required to diagnose EoE because of patchy distribution of esophageal eosinophils, it is unclear whether multiple biopsies are required to evaluate histological effectiveness of PPI therapy. This study aimed to determine the optimal biopsy protocol after PPI therapy in patients with EoE. METHODS: Of 110 EoE patients, 22 PPI nonresponders were enrolled. Intraepithelial eosinophils were counted in areas of high density in multiple biopsy specimens after PPI therapy. The prevalence of esophageal eosinophilia and peak eosinophil counts after PPI therapy was analyzed according to the biopsy sites and endoscopic findings. Positive predictive value (PPV) was calculated according to the number of biopsies. RESULTS: Of 124 biopsies, 59 (47.6%) specimens showed esophageal eosinophilia (≥15 per high-power field). Eosinophil counts were significantly higher in specimens from the lower esophagus than in those from the upper esophagus but not in those from the middle esophagus. Prevalence of esophageal eosinophilia was 76.2, 40.9, and 24.3% in the lower, middle, and upper esophagus respectively. PPI nonresponders were diagnosed in all cases with 4 biopsy specimens obtained from the lower and middle esophagus, showing that PPV for non-effectiveness of PPI therapy was 0.910 (95% CI 0.773-1.000). The prevalence of esophageal eosinophilia and peak eosinophil counts was higher in cases with white plaques and linear furrows. CONCLUSION: Multiple biopsies should be required to evaluate histological effectiveness of PPI therapy in patients with EoE. Four biopsies from the lower and middle esophagus may be sufficient.

Schwannoma-like tumor in the anterior cranial fossa immunonegative for Leu7 but immunopositive for Schwann/2E.

Schwannoma arising from the olfactory system, often called olfactory groove schwannoma (OGS), is rare, as the olfactory bulb and tract, belonging to the central nervous system, should lack Schwann cells. Another rare entity called olfactory ensheathing cell tumor (OECT) has been reported, which mimics clinical and radiological characteristics of OGS. Here, we report two rare cases of schwannoma-like tumor in the anterior cranial fossa that showed negative staining for Leu7, but positive staining for Schwann/2E, and discuss their origin. Two cases of mass lesions in the anterior cranial fossa in a 26-year-old man and a 24-year-old woman were successfully removed. Morphological examination of these tumors was compatible with a diagnosis of schwannoma. Immunohistochemically, both cases were negative for Leu7, yielding a diagnosis of OECT, but were positive for the schwannoma-specific marker, Schwann/2E. Immunohistochemical staining results in our two cases question the current assumption that OGS and OECT can be distinguished only by Leu7 staining pattern. In conclusion, the origins of OGS and OECT remain to be determined, and further studies in larger numbers of cases are needed to characterize these rare tumors in the anterior cranial fossa.

Feasibility of Cancer Immunotherapy with WT1 Peptide Vaccination for Solid and Hematological Malignancies in Children.

BACKGROUND: Advances in cancer immunotherapy in the pediatric field are needed in order to improve the prognosis of children with malignancies. We conducted a prospective phase I/II study of WT1 peptide vaccination for children with relapsed or refractory malignancies. METHODS: The main eligibility criteria were affected tissues or leukemic cells expressing the WT1 gene, and patients (and donors for allogeneic hematopoietic stem cell transplantation) having HLA-A*24:02. Vaccination using the WT1 peptide (CYTWNQMNL), which was modified for higher affinity to this HLA-type molecule with the adjuvant Montanide ISA51, was performed weekly 12 times. RESULTS: Twenty-six patients were enrolled and 13 (50.0%) completed the vaccination 12 times. Evidence for the induction of WT1-specific cytotoxic T-lymphocyte (CTL) responses without severe systemic side effects was obtained. Two out of 12 patients with bulky disease exhibited a transient clinical effect (one mixed response and one stable disease), three out of six patients with minimal residual disease achieved transient molecular remission, and five out of eight patients without a detectable level of the molecular marker, but with a high risk of relapse, had the best outcome of long-term continuous complete remission. CONCLUSIONS: WT1 vaccination is a safe immunotherapy and induced WT1-specific CTL responses in children; however, as a single agent, vaccination only provided patients in remission, but with a high risk of relapse, with "long-term benefits" in the context of its use for relapse prevention. WT1 peptide-based treatments in combination with other modalities, such as anti-tumor drugs or immunomodulating agents, need to be planned.

Carcinomatous meningitis from ovarian serous carcinoma: A case report.

Multifocal dissemination of cancer cells from the primary tumor sites to the subarachnoid, pia mater and cerebrospinal fluid (CSF) of the brain and spinal cord causes carcinomatous meningitis (CM). CM is rarely observed in patients with gynecological cancer. The present study described a 59-year-old woman who was diagnosed with CM as a recurrence of stage IIIC ovarian cancer, after presenting with headache and decreased level of consciousness. During adjuvant therapy following surgical debulking, she developed nausea and vomiting. The post-contrast fluid-attenuated inversion-recovery magnetic resonance imaging showed leptomeningeal enhancement on all sulci, particularly around the falx cerebri and cerebellar hemisphere. CM was suspected and CSF cytology revealed adenocarcinoma cells, thus confirming the diagnosis. Overall, although CM is rare, clinicians should be aware of this complication when patients with malignancies experience neurological symptoms, including headache, nausea and vomiting. Knowledge of this clinical entity should assist clinicians in ascertaining accurate diagnoses.

Two cases of eosinophilic gastrointestinal disorder due to newly appearing food allergies after cord blood transplantation.

Eosinophilic gastrointestinal disorders (EGIDs) are infrequent complications after allogeneic hematopoietic cell transplantation (allo-HCT). Furthermore, it is well-known that allergic diseases are transferable after allo-HCT from allergic donors to non-allergic recipients. However, the type of graft-versus host disease (GVHD) prophylaxis that leads to allergic disease transfer is unclear. Furthermore, no study has reported a case of acquired food allergy resulting in EGID that was detected based on the clinical course and the detection of antigen-specific immunoglobulin E after allo-HCT. We encountered two patients with acute leukemia accompanied by eosinophilic esophagitis (EoE) and eosinophilic gastroenteritis (EGE) due to newly appearing food allergy after cord blood transplantation (CBT) with T-cell non-depletion GVHD prophylaxis. Despite having no history of allergic disease, the patients experienced allergic symptoms due to dairy products (Case 1) and eggs (Case 2) after CBT. They subsequently experienced severe nausea, heartburn, and anorexia (Case 1) and diarrhea (Case 2). Cases 1 and 2 were diagnosed with EoE and EGE, respectively, based on endoscopic and histological examinations. Dietary treatment without steroids improved the symptoms in both cases. These cases highlight that the unexpected transfer of food allergy after CBT can lead to EGIDs, especially in patients receiving T-cell non-depletion GVHD prophylaxis.

Lustrous White Erosions Surrounded by an Erythematous Mucosa: A Novel Endoscopic Finding of Gastric Lesions in Patients with Wilson Disease.

Wilson disease is an inherited copper metabolism disorder. We herein report a novel endoscopic finding in three men with Wilson disease. These patients underwent upper endoscopy due to gastrointestinal symptoms or during follow-up. In each case, endoscopy revealed lustrous white erosions surrounded by an erythematous mucosa in the greater curvature of the gastric body. A biopsy of the lesions showed orcein-positive tissue, indicating copper deposition, in the interstitial stroma and fundic glands of the mucosa. All patients had been receiving treatment with zinc acetate. These endoscopic findings might have been related to the cytotoxicity of the accumulated copper and zinc acetate.

Meconium-related ileus in extremely low-birthweight neonates: etiological considerations from histology and radiology.

BACKGROUND: A nationwide survey on neonatal surgery conducted by the Japanese Society of Pediatric Surgeons has demonstrated that the mortality of neonatal intestinal perforation has risen over the past 15 years. The incidence of intestinal perforation in extremely low-birthweight (ELBW) neonates has been increasing as more ELBW neonates survive and as the live-birth rate of ELBW has increased. In contrast to necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP), the pathogenesis of meconium-related ileus, defined as functional bowel obstruction characterized by delayed meconium excretion and microcolon, remains unclarified. METHODS: The histology of 13 ELBW neonates with intestinal perforation secondary to meconium-related ileus was reviewed, and the radiology of 33 cases of meconium-related ileus diagnosed on contrast enema was reviewed. Specimens obtained from 16 ELBW neonates without gastrointestinal disease served as age-matched controls for histological assessment. RESULTS: The size of the ganglion cell nucleus in meconium-related ileus and in control subjects was 47.3 ± 22.0 µm(2) and 37.8 ± 11.6 µm(2), respectively, which was not significantly different. In all cases of meconium-related ileus, contrast enema demonstrated a microcolon or small-sized colon, with a gradual caliber change in the ileum and filling defects due to meconium in the ileum or colon, showing not-identical locations of caliber changes and filling defects. CONCLUSION: Morphological immaturity of ganglia was not suggested to be the pathogenesis of meconium-related ileus. Impaction of inspissated meconium is not the cause of obstruction, but the result of excessive water absorption in the hypoperistaltic bowel before birth, although the underlying mechanism responsible for the fetal hypoperistalsis remains unclear.

Pediatric giant cell reparative granuloma of the lower clivus: A case report and review of the literature.

Giant cell reparative granuloma (GCRG) is a benign nonneoplastic granulomatous lesion and is rare in the cranial bone. We present a pediatric case of this lesion arising from the condyle and lower clivus. A 9-year-old girl presented with slowly progressive hoarseness and dysphagia. She showed left glossopharyngeal, vagus, and hypoglossal nerve palsy. An osteolytic lesion around the lower clivus and condyle joint was accompanied by deformation of the craniovertebral junction. An endoscopic endonasal approach was used to decompress the cranial nerve and confirm the pathological finding. The lesion around the condyle was not resected to preserve occipito-cervical stability. The residual lesion has been observed carefully for 6 months, and regrowth has not occurred. GCRG is a rare granulomatous lesion in the cranial bone. This case is the first report of a pediatric clival GCRG. Treating pediatric GCRG may be helpful.

Intrahepatic cholangiocarcinoma with a tumor thrombus extending from the inferior vena cava to the right atrium: a case report.

BACKGROUND: Vascular invasion involving a tumor thrombus in the inferior vena cava and/or right atrium is an unfavorable prognostic factor after intrahepatic cholangiocarcinoma resection. We report an intrahepatic cholangiocarcinoma case with a tumor thrombus extending from the left hepatic vein via the inferior vena cava to the right atrium. CASE PRESENTATION: A 58-year-old man with epigastralgia was referred to our hospital after an emergent transcatheter arterial embolization was done following the radiological diagnosis of a ruptured hepatic tumor. The serum concentrations of carcinoembryonic antigen, carbohydrate 19-9, duke pancreatic monoclonal antigen type 2, and cytokeratin-19 fragments were elevated; meanwhile those of alfa-fetoprotein and des-γ-carboxy prothrombin were within normal ranges. A contrast-enhanced computed tomography scan showed a heterogeneously enhanced tumor, 13 cm in diameter, in the left lobe of the liver, enlarged lymph nodes along the lesser curvature of the stomach, and a tumor thrombus extending from the left hepatic vein via the inferior vena cava to the right atrium. We performed a left hemihepatectomy and tumor thrombectomy under total hepatic vascular exclusion to reduce the risk of sudden death. After dissection of the liver parenchyma along the left side of the middle hepatic vein, except for the left hepatic vein, the inferior vena cava just below the right atrium could be clamped by pulling down the left lobe of the liver toward the caudal side. The thrombus could be removed by incising the inferior vena cava under total hepatic vascular exclusion. Microscopic examination showed a tubular adenocarcinoma. Immunohistochemical staining was positive for cytokeratin-7, cytokeratin-19, and epithelial membrane antigen, but negative for arginase-1, glypican-3, and hepatocyte. The patient was pathologically diagnosed with an intrahepatic cholangiocarcinoma with a tumor thrombus in the inferior vena cava. Adjuvant chemotherapy with tegafur/gimeracil/oteracil was administered for 1 year. The patient remained in good health without cancer recurrence for over 4 years after the operation. CONCLUSION: An aggressive surgical approach may be indicated for intrahepatic cholangiocarcinoma with a tumor thrombus in the inferior vena cava and/or right atrium to avoid the risk of impending death.

IgG4-related mastitis requiring differentiation from breast cancer: a case report.

Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a group of chronic relapsing inflammatory conditions. Although IgG4-RD can occur in various organs, it is rarely observed in mammary glands. Here, we report a case of IgG4-related mastitis (IgG4-RM) that needed to be differentiated from breast cancer. A 54-year-old woman was examined for a tumor in her left breast. Mammary ultrasonography revealed an irregular hypoechoic tumor measuring 45.0 × 43.0 × 32.0 mm in size. A core-needle biopsy of the left breast tissue revealed a high degree of mixed T and B lymphocytic and plasma cell infiltration, as well as interstitial fibrosis. IgG4-RD was diagnosed based on hematological examination that revealed an abnormal IgG4 value of 332 mg/dl. All the clinical diagnostic criteria for IgG4 were met, resulting in a definitive diagnosis of IgG4-RM.

Breast Angiosarcoma with a Preoperative Diagnosis of Late Recurrence of Breast Cancer: A Case Report.

Angiosarcoma is a malignant mesenchymal tumor characterized by the presence of vascular endothelial cells. Although rare, angiosarcoma developing in the mammary glands has a poor prognosis. We report a case of breast angiosarcoma with a preoperative diagnosis of late recurrence of breast cancer. A 78-year-old woman noticed a tumor in her right breast and visited our hospital. The patient had undergone breast-conserving surgery and axillary lymph node dissection from the right breast 12 years before the visit. The tumor was diagnosed as T4bN0M0, stage IIIB. Anastrozole was administered as postoperative adjuvant therapy for 5 years; the patient also received 50-Gy whole-breast radiation therapy after surgery. Physical examination during her visit revealed an elevated lesion with blue purpura around the nipple in the right breast. We performed breast ultrasound and detected a well-defined 19.6 × 16.4 × 10.7 mm hypoechoic tumor in the left subareolar area. The patient underwent core needle biopsy (CNB). Based on the CNB specimen findings, she was suspected to experience late local recurrence after surgery. Therefore, she underwent total mastectomy after breast-conserving surgery. A dark-red tumor sized 18 × 12 mm was found in a specimen from the nipple. The pathological diagnosis of the specimen revealed short spindle-shaped tumor cells with strong nuclear pleomorphism and a significant interstitial fibrosis. Immunohistochemistry using D2-40 and CD31 antibodies showed irregular luminal proliferation at the anastomosis, infiltration into the surrounding tissue, and massive necrosis, thereby leading to the diagnosis of breast angiosarcoma. We have reported a case of breast angiosarcoma with a preoperative diagnosis of late recurrence of breast cancer.

Recurrence of Acute Lymphoblastic Leukemia with Bone Marrow Necrosis: A Case Report and Review of the Literature on the MRI Features of Bone Marrow Necrosis.

Bone marrow necrosis (BMN) is a rare but important complication of hematological malignancies. We report the case of a 52-year-old male patient with a recurrence of acute lymphoblastic leukemia (ALL) accompanied by BMN. After re-induction therapy, bone marrow aspiration (BMA) and biopsy from the iliac bone showed necrotic cells and eosinophilic debris, respectively. Magnetic resonance imaging (MRI) showed heterogeneous signals in the bilateral iliac bone, possibly reflecting various stages of BMN. BMA from the sternum eventually revealed the recurrence of ALL after a few weeks. Comprehensive assessments, including MRI and repeated bone marrow tests, are required when evaluating the underlying hematological malignancies of patients with BMN.

Change in morphology and oxytocin receptor expression in the uterine blood vessels during the involution process.

BACKGROUND: The histological changes in uterine blood vessels during pregnancy have been well investigated, but there have been few reports focusing on the changes in blood vessels during the involution process, especially within the first 24 h. We observed the process of uterine involution, focusing on the vessels of the resected uterus. METHODS: Paraffin-embedded uterine samples from 15 patients who underwent hysterectomy because of severe cervical laceration and uterine rupture were examined. The time between delivery and hysterectomy ranged from 15 min to 456 h. The specimens were stained with hematoxylin-eosin, elastica-van Gieson and an antioxytocin receptor antibody. RESULTS: Changes in the uterine vessels varied substantially based on their location. The intima in arteries of the endometrial side thickened within 5 h after delivery. On the serosal side, phlebosclerosis was demonstrated 6 weeks postpartum. Immunoreactivity for the oxytocin receptor (OTR) appeared in the muscular medias of arteries 5 h after delivery although it was not expressed before this period. CONCLUSION: Remodeling of uterine vessels involved thickening of the arterial intima and OTR expression in vessel walls during the first 5 h postpartum; the parameters normalized within 6 weeks. However, phlebosclerosis persisted for a long time on the serosal side.

Posterior fossa choroid plexus papilloma with focal ependymal differentiation in an adult patient: A case report and literature review.

Choroid plexus papillomas (CPPs) are rare neoplasms classified as World Health Organization grade I tumors. CPPs containing other tissues have occasionally been documented in the literature. However, few of these previous reports have provided clinical and radiological information. We herein report a case of a posterior fossa CPP with focal ependymal differentiation in a 42-year-old woman who presented with a 6-month history of progressive headache. Preoperative radiological images showed a hypervascular tumor protruding into the left foramen of Luschka with perilesional edema. Gross total resection of the tumor was performed. Histopathological examination revealed that the tumor was composed of papillary structures. Immunohistochemical staining of glial fibrillary acidic protein was focally positive around the capillaries, which was suggestive of "perivascular pseudorosette" formation. Our case showed similar imaging appearances as those of CPP; thus, it seems difficult to distinguish CPP with versus without ependymal differentiation by clinical and radiological features alone. The clinical significance and pathogenesis of ependymal differentiation in CPP remain unclear, and further case reports are required.

Clinicopathological Significance of Autophagy-related Proteins and its Association With Genetic Alterations in Gliomas.

AIM: To investigate clinicopathological significance of autophagy and its association with genetic alterations in gliomas. MATERIALS AND METHODS: The expression of three autophagy-related proteins, light chain-3 (LC3), beclin 1, and p62 was immunohistochemically analyzed in 32 low-grade gliomas and 65 high-grade gliomas. RESULTS: LC3, beclin 1, and p62 expression was positive in 70/94 (74%), 51/94 (54%) and 55/96 (57%) gliomas, respectively. High expression of LC3, beclin 1 and p62 was significantly more frequent in high-grade gliomas than in low-grade. Positive expression of LC3, beclin 1 and p62 were significantly positively correlated with overall survival, methylation of O6-methylyguanine-DNA methyltransferase (MGMT) promoter, mutations of isocitrate dehydrogenase 1 (IDH1) and telomerase reverse transcriptase (TERT) promoter, and 1p/19q co-deletion. Kaplan-Meier analyses revealed that LC3, p62 and autophagy status (positivity for at least two of the three proteins) were significantly associated with poorer survival. CONCLUSION: Autophagy might be associated with the progression of glioma, particularly high-grade, and thus might be a useful prognostic factor in patients with glioma.