Cytokine storm syndrome after anti-thymoglobulin infusion in a cynomolgus monkey with systemic lymphadenopathy caused by follicular hyperplasia: A case report.

Nonhuman primates are widely used in transplantation research as preclinical xeno- or allo-transplantation models. Rabbit anti-thymoglobulin (ATG) is often used for T-cell depletion as an immunosuppressant. T-cell depletion can cause a secondary cytokine storm syndrome that can be minimized/prevented by a prophylactic administration of systemic corticosteroids and antihistamines. We report a case of death due to CSS in a cynomolgus monkey with follicular hyperplasia-induced systemic lymphadenopathy after ATG administration. A 6-year-old female cynomolgus monkey was rendered diabetic and then transplanted with a genetically modified porcine pancreatic islets (PPI) (50 000 IEQ/kg) through the portal vein 22 days later without immunosuppressant. Because graft function was not comparable, we planned re-transplantation of PPI. For re-transplantation of the PPI, we performed an intravenous (IV) ATG infusion for inductive immunosuppression. The monkey died 3 h and 30 min after ATG administration despite cardiopulmonary resuscitation. Systemic lymphadenopathy was observed on submandibular, axillary, inguinal, foregut, colic, and hilar lymph nodes, and splenomegaly was also observed on necropsy. Histopathologic examination of the lymph node revealed follicular hyperplasia. The IL-6 level was higher after ATG infusion compared to before ATG infusion (before vs. after ATG infusion; 14.9 vs. >5000 pg/mL). The death of the cynomolgus monkey was caused by severe CSS because of apoptosis of B cells in the systemic lymph nodes caused by the ATG administration. A thorough physical examination of palpable lymph nodes and pre-ATG sonographic or computed tomographic screening could have identified lymphadenopathy, potentially preventing its infusion and reducing mortality risk.

MicroRNA 29a therapy for CEACAM6-expressing lung adenocarcinoma.

BACKGROUND: Non-coding microRNAs (miRNAs) play critical roles in tumor progression and hold great promise as therapeutic agents for multiple cancers. MicroRNA 29a (miR-29a) is a tumor suppressor miRNA that inhibits cancer cell growth and tumor progression in non-small cell lung cancer. Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), which plays an important role in lung cancer progression, has been identified as a target of miR-29a. Here, we evaluated the therapeutic efficacy of a peptide vector capable of delivering miR-29a intracellularly using the acidic tumor microenvironment in a lung adenocarcinoma xenograft mouse model. METHODS: A miRNA delivery vector was constructed by tethering the peptide nucleic acid form of miR-29a to a peptide with a low pH-induced transmembrane structure (pHLIP) to enable transport of the miRNAs across the plasma membrane. Tumor suppressive effects of pHLIP-miR29a on lung adenocarcinoma development in vivo were assessed using a BALB/c xenograft model injected with A549 cells. RESULTS: Incubation of A549 cells with pHLIP-miR-29a at an acidic pH downregulated endogenous CEACAM6 expression and reduced cell viability. Intravenous injection of the mice with pHLIP-miR-29a inhibited tumor growth by up to 18.1%. Intraperitoneal injection of cisplatin reduced tumor volume by 29.9%. Combined pHLIP-miR-29a + cisplatin treatment had an additive effect, reducing tumor volume up to 39.7%. CONCLUSIONS: Delivery of miR-29a to lung adenocarcinoma cells using a pHLIP-mediated method has therapeutic potential as a unique cancer treatment approach.

Altered Lung Heat Shock Protein-70 Expression and Severity of Sepsis-Induced Acute Lung Injury in a Chronic Kidney Disease Rat Model.

Enhanced heat shock protein-70 (HSP-70) expression in the lungs is associated with attenuated acute lung injury (ALI) in a sepsis model. Chronic kidney disease (CKD) significantly contributes to the poor prognosis of patients with sepsis. This study examined the relationship between sepsis-induced ALI severity and altered lung HSP-70 expression in CKD. Experimental rats underwent a sham operation (control group) or 5/6 nephrectomy (CKD group). Sepsis was induced with cecal ligation and puncture (CLP). Laboratory tests and lung harvest were performed in the control group (without CLP and after 3, 12, 24, and 72 h of CLP) and in the CKD group (without CLP and after 72 h of CLP). ALI was the most severe after 12 h of sepsis. The mean lung injury score at 72 h after sepsis was significantly higher in the CKD group than in the control group (4.38 versus 3.30, p < 0.01). Nonetheless, enhanced lung HSP-70 expression was not observed in the CKD group. This study shows that altered lung HSP-70 expression is associated with the worsening of sepsis-induced ALI in patients with CKD. Enhancing lung HSP-70 is a novel treatment target for patients with CKD and sepsis-induced ALI.

EML4-ALK V3 oncogenic fusion proteins promote microtubule stabilization and accelerated migration through NEK9 and NEK7.

EML4-ALK is an oncogenic fusion present in ∼5% of non-small cell lung cancers. However, alternative breakpoints in the EML4 gene lead to distinct variants of EML4-ALK with different patient outcomes. Here, we show that, in cell models, EML4-ALK variant 3 (V3), which is linked to accelerated metastatic spread, causes microtubule stabilization, formation of extended cytoplasmic protrusions and increased cell migration. EML4-ALK V3 also recruits the NEK9 and NEK7 kinases to microtubules via the N-terminal EML4 microtubule-binding region. Overexpression of wild-type EML4, as well as constitutive activation of NEK9, also perturbs cell morphology and accelerates migration in a microtubule-dependent manner that requires the downstream kinase NEK7 but does not require ALK activity. Strikingly, elevated NEK9 expression is associated with reduced progression-free survival in EML4-ALK patients. Hence, we propose that EML4-ALK V3 promotes microtubule stabilization through NEK9 and NEK7, leading to increased cell migration. This represents a novel actionable pathway that could drive metastatic disease progression in EML4-ALK lung cancer.

Acute aspiration pneumonia in common marmoset (Callithrix jacchus) with marmoset duodenal dilation syndrome: A case report.

A female common marmoset (Callithrix jachhus) suffered from weight loss exhibited tachypnea after anesthesia. We diagnosed marmoset duodenal dilation syndrome (MDDS) and aspiration pneumonia after post-anesthesia vomiting secondary to MDDS. If MDDS is suspected due to clinical symptoms such as weight loss, bloating, or vomiting, careful anesthesia and treatment of vomiting will be important to prevent aspiration pneumonia.

Clinicopathological Characteristics of Inflammatory Myositis Induced by COVID-19 Vaccine (Pfizer-BioNTech BNT162b2): A Case Report.

As more individuals were coronavirus disease 2019 (COVID-19) vaccinated, unexpected side effects appeared. Herein, we present the case of a 30-year-old man with myopathy in both extremities after the second dose of the Pfizer-BioNTech (BNT162b2) COVID-19 vaccine. Symptoms, swelling and pain, started from the proximal upper and lower extremities and extended to the distal parts. Although he underwent massive hydration, the muscle enzyme level continuously increased. He complained of dysphagia and dysarthria. Microscopically, muscle biopsy showed multifocal or scattered macrophage infiltration and degenerated myofibers. In contrast to general myopathy including inflammatory myositis and rhabdomyolysis, vaccine-induced inflammatory myositis shows a prolonged increase in muscle enzyme levels and multifocal macrophage infiltration with necrosis of the muscle fibers. Symptoms improved with glucocorticoid and immunosuppressive treatment. If vaccinated individuals experience severe and continuous muscle pain and swelling, clinicians should consider vaccine-induced inflammatory myositis, measure the muscle enzyme levels, and perform muscle biopsy for a definite diagnosis.

Characterization and comparison of genomic profiles between primary cancer cell lines and parent atypical meningioma tumors.

BACKGROUND: Meningiomas are the second most common primary tumors of the central nervous system. However, there is a paucity of data on meningioma biology due to the lack of suitable preclinical in vitro and in vivo models. In this study, we report the establishment and characterization of patient-derived, spontaneously immortalized cancer cell lines derived from World Health Organization (WHO) grade I and atypical WHO grade II meningiomas. METHODS: We evaluated high-resolution 3T MRI neuroimaging findings in meningioma patients which were followed by histological analysis. RT-qPCR and immunostaining analyses were performed to determine the expression levels of meningioma-related factors. Additionally, flow cytometry and sorting assays were conducted to investigate and isolate the CD133 and CD44 positive cells from primary atypical meningioma cells. Further, we compared the gene expression profiles of meningiomas and cell lines derived from them by performing whole-exome sequencing of the blood and tumor samples from the patients, and the primary cancer cell lines established from the meningioma tumor. RESULTS: Our results were consistent with earlier studies that reported mutations in NF2, SMO, and AKT1 genes in atypical meningiomas, and we also observed mutations in MYBL2, a gene that was recently discovered. Significantly, the genomic signature was consistent between the atypical meningioma cancer cell lines and the tumor and blood samples from the patient. CONCLUSION: Our results lead us to conclude that established meningioma cell lines with a genomic signature identical to tumors might be a valuable tool for understanding meningioma tumor biology, and for screening therapeutic agents to treat recurrent meningiomas.

Analysis of EGFR mutation status in malignant pleural effusion and plasma from patients with advanced lung adenocarcinoma.

Background: Cell-free DNA (cfDNA) is emerging as a surrogate sample type for mutation analyses. We investigated the suitability of malignant pleural effusion (MPE) and plasma as a biomaterial for analyzing epidermal growth factor receptor (EGFR) mutation by peptide nucleic acid (PNA) clamping-assisted fluorescence melting curve (PANAMutyper™) analysis. Methods: Matched tissue, MPE cell block (MPE-CB), MPE supernatant, and plasma samples were collected from patients with advanced lung adenocarcinoma who had a MPE at the time of diagnosis. EGFR mutation was assessed by PANAMutyper™. Results: Mutation analyses in matched tumor tissues, MPE-CB, MPE supernatant, and/or plasma samples were available for 67 patients. In comparison with tumor tissue and MPE-CB, MPE supernatant exhibited 84.4% sensitivity, 97.1% specificity, 96.4% positive predictive value (PPV), and 87.2% negative predictive value (NPV). In the same comparison, plasma exhibited 70.6% sensitivity, 100.0% specificity, 100.0% PPV, and 73.7% NPV. When sorted by mutation type, MPE supernatant had better sensitivity than plasma for the detection of two major EGFR mutations: 93.8% vs. 75.0% for exon 19 deletion and 73.3% vs. 60.0% for L858R. Conclusions: In this cohort of patients with MPEs, MPE supernatant demonstrated superior diagnostic performance compared with plasma using a PNA-based real-time PCR method.

Discordance in HER2 status between primary gastric adenocarcinoma tumors and cells from the corresponding malignant effusions.

BACKGROUND: Metastasis of gastric cancer commonly manifests as a malignant effusion, which presents an alternative cell source for human epidermal growth factor receptor 2 (HER2) status identification. This study aimed to compare HER2 status in primary gastric adenocarcinoma tumors and corresponding cell blocks prepared from malignant effusions (CB-MEs). METHODS: HER2 status was retrospectively evaluated by immunohistochemistry (IHC) in primary gastric adenocarcinomas and paired pathologically confirmed CB-MEs of 45 patients. Silver in situ hybridization (SISH) was also performed in cases with IHC 2+ for primary gastric adenocarcinomas and above IHC 1+ for CB-MEs. RESULTS: HER2 positivity was observed in 4.4% (2/45) of primary gastric adenocarcinomas and 6.7% (3/45) of CB-MEs. The HER2 concordance rate between primary gastric adenocarcinomas and CB-MEs was 88.9% (40/45) (κ = - 0.056). All five patients with HER2 positivity in the primary tumor or a CB-ME had a negative result in the corresponding paired sample. Of the 15 patients with two or more serially sampled CB-MEs, HER2 expression determined by IHC differed between each CB-ME in six (40%) patients, and all three patients with HER2 positivity in CB-MEs exhibited HER2 positivity in one of the serially sampled CB-MEs. CONCLUSIONS: The HER2 positivity rate was very low in gastric cancer patients with malignant effusions. Our results suggest that HER2 positivity was discordant between the primary gastric adenocarcinoma and corresponding CB-MEs and among serially sampled CB-MEs. The possibility of detecting HER2 positivity can be improved if the primary gastric adenocarcinoma tumor as well as all the available CB-MEs from each patient are analyzed.

Carcinosarcoma of the parotid gland with abdominal metastasis: a case report and review of literature.

BACKGROUND: Carcinosarcoma of the salivary gland is a rare aggressive malignant tumor, composed of a mixture of carcinomatous and sarcomatous components. The most common metastatic sites include the lungs, bones, and central nervous system. CASE PRESENTATION: This report describes a rare case of carcinosarcoma of the parotid gland with an osteosarcoma as sarcomatous component in a 72-year-old man who had a history of low anterior resection for rectal cancer. Six months after parotidectomy, he presented abdominal pain as a symptom of abdominal metastasis by the sarcomatous component. At that time, the possibility of abdominal metastasis was overlooked because of the history of abdominal surgery. After several days of conservative treatment, emergency laparotomy was done. However, he died of acute respiratory distress syndrome. CONCLUSIONS: Awareness of the possibility of abdominal metastasis by salivary carcinosarcoma may help in managing patients with a history of abdominal surgery.

Extra-articular tenosynovial giant cell tumor of diffuse type in the temporal area with brain parenchymal invasion: a case report.

Tenosynovial giant cell tumor of diffuse type is a locally aggressive neoplasm that most commonly arises in the lower extremities. Herein, we report for the first time a case of an extra-articular tenosynovial giant cell tumor of diffuse type in the temporal region with brain parenchymal invasion. Imaging studies revealed an intracranial expansile mass in the temporal bone without involvement of the temporomandibular joint. The unusual location of the tumor without involvement of the joint and the presence of brain parenchymal invasion made this case challenging to diagnose.

Clear cell neuroendocrine tumor of the pancreas in von Hippel-Lindau disease: a case report and literature review.

Clear cell neuroendocrine tumor (NET) of the pancreas is found in von Hippel-Lindau (VHL) disease, multiple endocrine neoplasia type I (MEN I), and sporadic form. Clear cell NETs are often misdiagnosed as metastatic renal cell carcinoma. A 47-year-old woman with VHL was found to have a mass in the pancreatic tail and two masses in the right kidney with two cysts. A distal pancreatectomy and right radical nephrectomy were performed. The pancreatic lesion was a well-circumscribed, golden-yellow solid mass, which was lobulated by septal fibrosis. Microscopically, the tumor consisted of entirely of clear cells with prominent nucleoli. The tumor cell nests were separated by collagen fibrosis. Immunohistochemical studies were positive for the neuroendocrine markers and vimentin. Synchronous kidney tumors were clear cell renal cell carcinoma and cystic renal cell carcinoma. Those with syndrome are younger than those without syndrome. Sporadic tumors have larger size and higher grade than those of VHL and MEN I. Stromal sclerosis is frequently observed in VHL, compared with the other two groups. In the absence of a documented genetic profile and family history, awareness of these features should help us to diagnose clear cell pancreatic NETs resembling metastatic renal cell carcinoma.

Cauda equina lymphoma mimicking non-neoplastic hypertrophic neuropathy of the cauda equina: A case report.

Spinal cauda equina lymphoma (CEL) is very rare, with only about 14 cases reported in the English medical literature. Magnetic resonance image findings and the gross appearance of CEL at surgery are similar to those of non-neoplastic hypertrophic neuropathy of the cauda equina (HNCE); however, their prognosis and treatment are very different. We report a case of CEL and discuss the differences from non-neoplastic HNCE.

Clinicopathological Significance of Minimal Extrathyroid Extension in Solitary Papillary Thyroid Carcinomas.

BACKGROUND: The definitive diagnosis of minimal extrathyroid extension (ETE) is subjective because a well-defined true capsule is absent in the thyroid gland. We subclassified the extent of minimal ETE and investigated the clinicopathological significance of the presence of minimal ETE in patients with solitary papillary thyroid carcinomas (PTCs) and solitary papillary thyroid microcarcinomas (PTMCs). METHODS: A series of 546 patients with solitary PTCs, including 144 patients with solitary PTMCs, were retrospectively analyzed. Whether the presence of minimal ETE had an effect on recurrence-free survival (RFS) along with other clinicopathological parameters was investigated. RESULTS: The only independent prognostic factor found to be associated with recurrence was the presence of LN metastasis in solitary PTC (p = 0.002) but not in solitary PTMC groups (p = 0.073). The presence of minimal ETE had no effect on RFS in both solitary PTC (p = 0.053) and solitary PTMC (p = 0.816). CONCLUSIONS: The presence of minimal ETE has no significant influence on RFS in solitary PTC and PTMC. There is a risk of overrepresenting the T3 category in solitary PTC and PTMC patients with minimal ETE.

Effectiveness of adjuvant radiotherapy after local excision of rectal cancer with deep submucosal invasion: a single-hospital, case-control analysis.

BACKGROUND: The role of postoperative radiation therapy (RT) after local excision (LE) of deep submucosal invasive rectal cancer remains unclear. We evaluated the efficacy of adjuvant RT after LE of early rectal cancer with deep submucosal invasion. METHODS: We screened 227 patients who underwent transanal excision or endoscopic removal of deep submucosal invasive rectal cancer between 1992 and 2012, of which 66 did not undergo radical surgery owing to the patient's preference or poor medical conditions. Of these, 35 (53 %) underwent LE alone (LE group) and 31 (47 %) received adjuvant RT after LE (LE + RT group). Nine patients in the RT group received concurrent adjuvant chemotherapy with 5-fluorouracil. Two independent pathologists reviewed histological data. RESULTS: The mean age of patients in the LE + RT and LE groups was 59.5 ± 9.6 and 55.3 ± 11.2 years, respectively. The mean follow-up duration was 78.7 ± 66.7 months in the LE + RT group and 70.5 ± 45.7 months in the LE group. Cancer eventually recurred in six patients (9.1 %; two in the LE + RT group and four in the LE group). In five of these patients, recurrence occurred within 4 years after the initial treatment. The other patient, who was in the LE group, exhibited multiple lymph node metastases at the 116-month follow-up. Kaplan-Meier estimates of recurrence-free survival at 5 years after treatment were 96.8 % in the LE + RT group and 97 % in the LE group (P = 0.657). CONCLUSION: RT after LE of early rectal cancer with deep submucosal invasion might not improve recurrence-free survival compared with LE alone.

Epithelioid angiomyolipoma of the liver in a patient with Li-Fraumeni syndrome: a case report.

BACKGROUND: Epithelioid angiomyolipoma (EAML) is a rare variant of angiomyolipoma that predominantly consists of epithelioid cells and belongs to the perivascular epithelioid cell neoplasm (PEComa) family. The majority of EAMLs arise in the kidneys, and primary hepatic EAML appears to be much less common than renal EAML. Most PEComas arise sporadically, but may be associated with tuberous sclerosis complex (TSC), an autosomal dominant genetic disorder characterized by germline mutations in the TSC1 or TSC2 genes. However, PEComas have previously been reported in five patients with Li-Fraumeni syndrome (LFS), which is an inherited cancer susceptibility disorder resulting from germline mutations in the TP53 tumor suppressor gene. CASE PRESENTATION: We report a 49-year-old female patient with hepatic EAML and pancreatic cancer. Because she had previously been diagnosed with bilateral breast cancer at the age of 30, we performed a comprehensive genetic analysis to identify genetic alterations associated with any cancer predisposition syndrome. Whole-exome sequencing of a blood sample identified a heterozygous germline variant of TP53 (NM_000546.5):c.708C>A, and targeted next-generation sequencing of liver EAML and pancreatic cancer tissue samples demonstrated the same TP53 (NM_000546.5):c.708C>A variant in both. This, plus the patient's history of early-onset breast cancer, met the 2015 version of the Chompret criteria for diagnosis of LFS. CONCLUSIONS: There have been very few case reports regarding the presence of PEComa in LFS, and to the best of our knowledge, this is the first report of EAML of the liver in a patient with LFS.

Absence of enhancement in a lesion does not preclude primary central nervous system T-cell lymphoma: A case report.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a non-Hodgkin lymphoma that originates in the central nervous system (CNS) and is exclusively limited to the CNS. Although most PCNSLs are diffuse large B-cell lymphomas, primary CNS T-cell lymphomas (PCNSTLs) are rare. PCNSTLs typically demonstrate some degree of enhancement on contrast-enhanced magnetic resonance imaging (MRI). To the best of our knowledge, non-enhancing PCNSTL has not been reported previously. CASE SUMMARY: A 69-year-old male presented to the neurology department with complaints of mild cognitive impairment and gradual onset of left lower leg weakness over a span of two weeks. Initial MRI showed asymmetric T2-hyperintense lesions within the brain. No enhancement was observed on the contrast-enhanced T1 image. The initial diagnosis was neuro-Behçet's disease. Despite high-dose steroid therapy, no alterations in the lesions were identified on initial MRI. The patient's symptoms deteriorated further. An MRI performed one month after the initial scan revealed an increased lesion extent. Subsequently, brain biopsy confirmed the diagnosis of PCNSTL. The patient underwent definitive combined chemo-radiotherapy. However, the patient developed bacteremia and died of septic shock approximately three months after diagnosis. CONCLUSION: The absence of enhancement in the lesion did not rule out PCNSTL. A biopsy approach is advisable for pathological confirmation.

Diagnostic Value of Nestin Expression in Adult Gliomas.

Introduction. Nestin, a type VI intermediate filament, is expressed in neuroepithelial cells during embryogenesis and has been expressed in various human tumors. Recent studies reported that the expression was associated with poor prognosis in brain tumors, but the results were inconclusive. In this study, we evaluated usefulness of nestin expression as a prognostic biomarker in consideration of IDH mutation and the World Health Organization (WHO) classification fifth edition. Methods. To investigate nestin expression, immunohistochemistry was performed on 92 adult brain gliomas using tissue microarrays. We analyzed the clinical characteristics and survival outcomes according to nestin expression and examined whether nestin expression alone affects the prognosis, independent of IDH mutation. Results. Sixty patients (65.2%) were nestin-positive (weak and strong). Nestin expression and intensity were significantly correlated with pathologic diagnosis and IDH mutation. The patients with high-grade gliomas showed a higher frequency and stronger intensity of nestin expression than those with low-grade gliomas (P < .001). The majority (93.6%) of gliomas with IDH mutation showed no expression or weak positivity. Multivariate Cox proportional hazard regression analysis for overall survival demonstrated that nestin expression (weak, hazard ratio [HR] 5.39, P = .036; strong, HR 8.43, P = .007) was an independent prognostic factor. Moreover, patients with nestin-expressing glioma showed shorter survival (P < .001). Conclusions. Nestin seems to be strongly expressed in the vast majority of glioblastomas, IDH-wildtype and rarely in IDH-mutant gliomas. Clear correlation between nestin expression and pathologic diagnosis makes an accurate patient diagnosis. Expression and intensity of nestin were significantly correlated with worse survival.

Adenocarcinoma arising from heterotopic pancreas at the first portion of the duodenum: a case report.

Malignant transformation of a heterotopic pancreas in the duodenum is very rare. To our knowledge, only 15 cases have been reported worldwide, including the present case. We herein report a rare case of malignant transformation of a heterotopic pancreas in the duodenum along with a review of the literature.A 65-year-old man was admitted to our hospital for evaluation of dyspepsia and vomiting. Esophagogastroduodenoscopy showed a stricture of the duodenal bulb. Laparoscopic distal gastrectomy was performed. Although a duodenal tumor had not been suspected, histopathological examination of the surgical specimen showed adenocarcinoma arising from a heterotopic pancreas (Heinrich type III) in the duodenum. Four months postoperatively, the patient received adjuvant chemotherapy. He was still alive without recurrence at 24 months of follow-up.Adenocarcinoma arising in a heterotopic pancreas is rare; therefore, preoperative diagnosis is difficult to obtain. Effective management of a heterotopic pancreas depends on the presence or absence of symptoms. Awareness of the possibility of malignant change in a heterotopic pancreas of the duodenum prior to surgery is helpful for the diagnosis and appropriate management of such patients.

pSlugS158 Immunohistochemistry is Useful in Grading Meningioma.

Snail family transcriptional repressor 2 (SNAI2, Slug) is a transcription factor that belong to the Slug/Snail superfamily. Site specific phosphorylation of slug (pSlugS158) is detected during the M phase, and thus, this phosphorylated protein is considered a novel marker for detecting mitotic figures. Herein, we investigated whether the detection of mitosis using pSlugS158 expression can be used in the histological grading of meningioma. We performed immunohistochemistry for pSlugS158 and PHH3 in tissue samples of 61 patients with meningioma and examined the association between mitotic counts using pSlugS158 and recurrence-free survival (RFS). The nuclear expression of pSlugS158 was observed in the cell with mitotic figures. Tumor grading based on pSlugS158 was significantly associated with the RFS (p < .001). It can be concluded that pSlugS158 is a useful and practical marker to detect mitosis and seems to be reliable for the counting of mitoses in histological grading of meningioma.