Dynamic CT and Gadoxetic Acid-enhanced MRI Characteristics of P53-mutated Hepatocellular Carcinoma.

Background Imaging markers of hepatocellular carcinoma (HCC) on the basis of molecular classification are important for predicting malignancy grade and prognosis. P53-mutated HCC is a major aggressive subtype; however, its imaging characteristics have not been clarified. Purpose To clarify the imaging characteristics of P53-mutated HCC at dynamic CT and gadoxetic acid-enhanced MRI that are correlated with its clinical features, pathologic findings, and prognosis. Materials and Methods In this retrospective single-center study, patients with surgically resected HCC between January 2015 and May 2018 in a university hospital were evaluated. HCC was classified into P53-mutated HCC and non-P53-mutated HCC using immunostaining. Dynamic CT and gadoxetic acid-enhanced MRI findings, clinical features, pathologic findings, and prognosis were compared using Mann-Whitney test, χ2 test, multivariable regression analysis, receiver operating characteristic analysis, Kaplan-Meier method, and log-rank test. Immunohistochemical expression of P53, organic anion transporting polypeptide 1B3 (OATP1B3), and CD34 were evaluated, and the correlations were analyzed using the Pearson correlation test. Results In total, 149 patients (mean age, 67 years ± 9 [SD]; 103 men) with 173 HCCs were evaluated. P53-mutated HCC (n = 28) demonstrated higher serum α-fetoprotein (median, 127.5 ng/mL vs 5.5 ng/mL; P < .001), larger size (40.4 mm ± 29.7 vs 26.4 mm ± 20.5; P = .001), and higher rates of poorly differentiated HCC (22 of 28 [79%] vs 24 of 145 [17%]; P < .001). Dilated vasculature in the arterial phase of dynamic CT (odds ratio, 14; 95% CI: 3, 80; P = .002) and a lower relative enhancement ratio in the hepatobiliary phase (odds ratio, 0.05; 95% CI: 0.01, 0.34; cutoff value, 0.69; P = .002) independently predicted P53-mutated HCC. OATP1B3 expression and P53 expression were inversely correlated (P = .002; R = -0.24). Five-year overall survival was worse for P53-mutated HCC (50.0% vs 72.6%; P = .02). Conclusion Dilated vasculature at the arterial phase of dynamic CT and a lower relative enhancement ratio at the hepatobiliary phase of gadoxetic acid-enhanced MRI were useful markers for P53-mutated hepatocellular carcinoma with poor prognosis. © RSNA, 2022 Online supplemental material is available for this article.

Presence of identical B-cell clone in both cerebrospinal fluid and tumor tissue in a patient with opsoclonus-myoclonus syndrome associated with neuroblastoma.

Opsoclonus-myoclonus syndrome associated with neuroblastoma (OMS-NB) is a refractory paraneoplastic syndrome which often remain neurological sequelae, and detailed pathogenesis has remained elusive. We encountered a pediatric patient with OMS-NB treated by immunosuppressed therapy who showed anti-glutamate receptor δ2 antibody and increased B-cells in cerebrospinal fluid (CSF), and multiple lymphoid follicles containing abundant Bcells in tumor tissue. Unbiased B-cell receptor repertoire analysis revealed identical B-cell clone was identified as the dominant clone in both CSF and tumor tissue. These identical B-cell clone may contribute to the pathogenesis of OMS-NB. Our results could facilitate the establishment of pathogenesis-based treatment strategies for OMS-NB.

Notch-Hes1 signaling activation in Caroli disease and polycystic liver disease.

The Notch signaling pathway plays a key role in the morphogenesis of the biliary tree, but its involvement in cystic biliary diseases, such as Caroli disease (CD) and polycystic liver disease (PLD), has yet to be determined. Immunostaining was performed using liver sections of CD and PLD, and the results were compared with those of congenital hepatic fibrosis (CHF) and von Meyenburg complex (VMC). The expression of Notch receptor 1 (Notch1) was increased in the nuclei of biliary epithelial cells in all cases of CD and PLD, whereas it remained at a low level in CHF and VMC. In addition, Notch2 and Notch3 were preferably expressed in the nuclei of biliary epithelial cells of PLD. Accordingly, the Notch effector Hes1 was highly expressed in biliary epithelial cells of CD and PLD, and the cell proliferative activity was significantly higher in CD and PLD. The expression of the Notch ligand Delta-like 1 was significantly increased in biliary epithelial cells of CD and PLD, which may be causally associated with the nuclear overexpression of Notch1 and Hes1. These results indicate that aberrant activation of the Notch-Hes1 signaling pathway may be responsible for the progression of biliary cystogenesis in CD and PLD.

Rhabdomyosarcoma arising from retroperitoneal teratoma in an infantile neurofibromatosis type 1 patient.

We herein report the case of a 2-year-old girl with neurofibromatosis type 1 (NF1), who presented with a 12-cm mass in the right retroperitoneum and underwent tumor resection. Histologically, the tumor was composed of two distinct components: one was teratoma, showing mature morphology; and the other was embryonal rhabdomyosarcoma. An interphase fluorescence in situ hybridization (FISH) analysis of the rhabdomyosarcoma component revealed the absence of isochromosome 12p. Although it is well known that rhabdomyosarcoma occurs in infantile NF1, and that rhabdomyosarcoma can arise from teratoma as a somatic-type malignancy, to the best of our knowledge, this is the first case of an infantile NF1 patient, who developed rhabdomyosarcoma within a retroperitoneal teratoma. The absence of chromosome 12p alteration suggests a possibility that the rhabdomyosarcoma occurred due to the NF1 background, not as a somatic-type malignancy of germ cell tumor.

The Combination Of Weak Expression Of PRDX4 And Very High MIB-1 Labelling Index Independently Predicts Shorter Disease-free Survival In Stage I Lung Adenocarcinoma.

Background: Oxidative stress plays pivotal roles in the progression of lung adenocarcinoma (LUAD) through cell signaling related closely to cancer growth. We previously reported that peroxiredoxin 4 (PRDX4), a secretory-type antioxidant enzyme, can protect against the development of various diseases, including potential malignancies. Since many patients with early-stage LUAD develop recurrence, even after curative complete resection, we investigated the association of the PRDX4 expression with the clinicopathological features and recurrence/prognosis using post-surgical samples of stage I-LUAD. Methods: The expression of PRDX4 and MIB-1, a widely accepted Ki67 protein, was immunohistochemically analysed in 206 paraffin-embedded tumour specimens of patients with stage I-LUAD. The PRDX4 expression was considered to be weak when less than 25% of the adenocarcinoma cells showed positive staining. Results: A weak PRDX4+ expression demonstrated a significantly close relationship with pathologically poor differentiation, highly invasive characteristics and recurrence. The decrease in PRDX4-positivity potentially induced cell growth in LUAD, which was correlated significantly with a very high MIB-1 labelling index (≥17.3%). Univariate/multivariate analyses revealed that the subjects with both weak PRDX4+ expression and a very high MIB-1 index had significantly worse disease-free survival rates than other subjects. Conclusions: The combination of weak PRDX4 expression and a very high MIB-1 index can predict high proliferating activity and recurrence with a potential poor prognosis, especially in post-operative stage I-LUAD patients.

Narrow band imaging-guided endoscopic biopsy for intraventricular and paraventricular brain tumors: clinical experience with 14 cases.

BACKGROUND: Narrow-band imaging (NBI) has been confirmed as a useful endoscopic technique to distinguish neoplasm from normal tissue, on the basis of the enhanced neovascularity of tumor tissue. NBI-guided tissue biopsy for laryngopharyngeal and digestive lesions is a novel methodology, but the feasibility for central nervous system tumors remains unclear. The aim of our study was to evaluate the feasibility of NBI-guided biopsy for intraventricular and paraventricular tumor. METHODS: Fourteen patients with intraventricular or paraventricular tumors underwent neuroendoscopic biopsy using a videoscope with NBI. Ventricular walls and tumors were observed using conventional imaging, followed by NBI. Colors of ventricle walls and tumors visualized using NBI were compared to those visualized under conventional imaging. Extracted specimens were stained using CD31 antibody and numbers of microvessels in each specimen were counted for analyzing vascular density. RESULTS: Normal ventricle walls were a similar color under conventional imaging and NBI. Tumor surfaces appeared to be cyan in color under NBI. Vessels on the tumor were more clearly visualized with NBI than with conventional imaging. NBI was able to identify tumor surfaces that were not perceptible on conventional imaging. All specimens in the lesion surfaces from cyan-colored areas under NBI contained tumor cells. Specimens extracted from regions that appeared cyan in color under NBI (51.0 vessels/mm(2)) had significantly greater vascular density than regions that appeared a normal color (17.4 vessels/mm(2); p = 0.039). CONCLUSION: NBI-guided biopsy of intraventricular and paraventricular tumors is feasible for visualizing tumor surface-enhancing neovascularities. NBI would contribute to accurate histological diagnosis while minimizing injury to surrounding structures.

Recurrence of an extracranial internal carotid artery aneurysm treated with STA-MCA bypass and trapping due to neovascularization from an ascending pharyngeal artery: illustrative case.

BACKGROUND: Extracranial internal carotid artery aneurysms (EICAs) are rare. Although a high mortality risk has been reported in nonoperated cases, the optimal treatment for EICAs remains unknown. OBSERVATIONS: A 79-year-old female presented with painless swelling in the right neck. Imaging revealed a giant EICA with a maximum diameter of 3.2 cm. Superficial temporal artery-middle cerebral artery bypass and internal carotid artery (ICA) trapping were performed. Because the distal aneurysm edge was at the C1 level, the distal portion of the aneurysm was occluded by endovascular coiling, and the proximal portion was surgically ligated. Blood flow into the aneurysm disappeared after the operation. Three years postsurgery, enlargement of the aneurysm with blood flow from the ascending pharyngeal artery (APA) was detected. The EICA was resected after coiling the APA and ligating both ends of the aneurysm. Pathologically, neovascularization within the aneurysm wall was observed. LESSONS: Even if blood flow into an EICA disappears after ICA trapping, the EICAs can enlarge due to neovascularization from the neighboring artery. From the outset, removal of the aneurysm should be considered as a radical treatment strategy for giant EICAs.

α-SMA positive vascular mural cells suppress cyst formation in hemangioblastoma.

Approximately 60% of hemangioblastomas (HBs) have peritumoral cysts adjacent to the tumor, which can cause neurological deficits due to the mass effect, and the management of cyst formation is a clinical challenge. Vascular mural cells surrounding endothelial cells consist of vascular smooth muscle cells (vSMCs) and pericytes, which are essential elements that support blood vessels and regulate permeability. This study investigated the involvement of mural cells in cyst formation. We analyzed the expression of α-smooth muscle actin (α-SMA), platelet-derived growth factor receptor-beta (PDGFRB), and CD31 in 39 consecutive human cerebellar HBs, 20 of cystic and 19 of solid type. Solid type HBs showed stronger diffuse expression of α-SMA in precapillary arterioles and capillaries within the tumor than cystic type HBs (p = 0.001), whereas there was no difference in PDGFRB and CD31 expression. Detailed observation with immunofluorescence demonstrated that α-SMA was expressed in vascular mural cells surrounding capillaries in the solid rather than in the cystic type. Multivariate analysis including various clinical and pathological factors showed that lower α-SMA expression was significantly correlated with cyst formation (p < 0.001). Our data suggested that vascular mural cells from precapillary arterioles to capillaries expressing α-SMA may be pericytes and play a crucial role in HB cystogenesis.

Dural metastasis from prostate carcinoma mimicking tuberculum sellae meningioma: A case report.

Background: Prostate carcinoma rarely metastasizes to the central nervous system. However, when it does, a dural lesion is a common and possible misdiagnosis of meningioma. Here, we describe a case of a 77-year-old man with dural metastasis from prostate carcinoma of the tuberculum sellae. Case Description: The patient was diagnosed with prostate carcinoma 7 years previously and was well-controlled by hormone therapy. He was incidentally found to have a suprasellar tumor and underwent endoscopic endonasal transsphenoidal surgery because of rapid tumor growth and worsening visual impairment. Since his serum prostate-specific antigen (PSA) level was within the normal range, malignant meningioma was suspected based on the magnetic resonance imaging (MRI) and the course. However, the pathological findings revealed dural metastasis from prostate carcinoma. He received radiation therapy, and the tumor disappeared on MRI. His visual impairment improved without recurrence. This case report highlights that dural metastasis of the tuberculum sellae arose despite the patient's PSA level being within the normal range, and a single metastasis to the dura was found. Conclusion: In patients with a history of prostate carcinoma or older men, careful follow-up considering the possibility of metastasis is required when a dural lesion is found.

Case report: Rosai-Dorfman disease with rare extranodal lesions in the pelvis, heart, liver and skin.

Rosai-Dorfman disease (RDD), a rare form of non-Langerhans cell histiocytosis, can involve systemic extranodal lesions. Skin lesions are the most common, whereas intrapelvic, cardiac, and hepatic lesions are infrequent. The present study describes a 74-year-old woman with multiple extranodal lesions in the pelvis, heart, liver, and skin that were successfully treated with glucocorticoid therapy. She had experienced fever and persistent inflammation without cervical lymphadenopathy for several months and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) showed abnormal FDG uptake in the left cheek; cervical, axillary, inguinal lymph nodes; periatrium; and pelvis. She was diagnosed with RDD based on skin and pelvic biopsies. Although this was an atypical case without bilateral cervical lymphadenopathy, the FDG-PET detection of inflammatory lesions led to selection of suitable biopsy sites, and pathological examination led to a correct diagnosis. Findings in this patient indicate that RDD can present with an atypical distribution of infrequent extranodal lesions, with attention required to prevent a delayed diagnosis.

Unusual local and distant metastases after complete resection of roentgenographically occult squamous cell carcinoma.

Roentgenographically occult squamous cell carcinoma (ROSCC) was reported to have been cured after complete resection. We experienced unusual local and distant metastases after complete resection of a ROSCC of left B6 bronchus. During the operation due to the proximal bronchial stump being positive for squamous cell carcinoma (SCC), a left lower sleeve lobectomy was performed. Six years after the operation, a chest CT showed no abnormal shadows. 6 months later a PET-CT showed metastases on bilateral supraclavicular lymph nodes, mediastinal lymph nodes, and the right adrenal glands. A biopsy of the right supraclavicular lymph node revealed that it was a metastatic SCC. The possibility of recurrence from a second pulmonary SCC might still remain. A prolonged follow-up over many years is desirable for a heavy smoker with a ROSCC.

Gastrointestinal stromal tumor metastasis to the ovary: A case report.

Gastrointestinal stromal tumors are common mesenchymal tumors of the gastrointestinal tract. The major site of metastasis for gastrointestinal stromal tumors is the liver or peritoneum, while metastasis to the ovary is exceptionally rare. A 53-year-old woman visited the hospital for bloating and anorexia and was diagnosed with a huge gastric gastrointestinal stromal tumor and peritoneal metastasis in the pelvis on upper gastrointestinal endoscopy and abdominal enhanced computed tomography. After administration of imatinib, the tumor was significantly reduced, and we performed laparoscopic pelvic tumor resection and open proximal gastrectomy with transverse colectomy. Intraoperatively, the pelvic tumor was found to be an ovarian tumor. Microscopic examination confirmed a gastric gastrointestinal stromal tumor with ovarian metastasis. In conclusion, we experienced a rare case of gastric gastrointestinal stromal tumor with ovarian metastasis. Preoperative administration of imatinib was successful and radical resection was achieved. Although pelvic tumors are difficult to differentiate preoperatively, the possibility of ovarian metastasis from gastrointestinal stromal tumor should be considered.

The phosphorylation of ephrin-B2 ligand promotes glioma cell migration and invasion.

To reveal molecular drivers of glioma invasion, two distinct glioblastoma (GBM) cell phenotypes (invading cells and tumor core cells) were collected from 19 GBM specimens using laser capture microdissection. Isolated RNA underwent whole human genome expression profiling to identify differentially expressed genes. Pathway enrichment analysis highlighted the bidirectional receptor/ligand tyrosine kinase system, EphB/ephrin-B, as the most tightly linked system to the invading cell phenotype. Clinical relevance of ephrin-B genes was confirmed in a clinically annotated expression data set of 195 brain biopsy specimens. Levels of ephrin-B1 and -B2 mRNA were significantly higher in GBM (n = 82) than in normal brain (n = 24). Kaplan-Meier analysis demonstrated ephrin-B2, but not ephrin-B1, expression levels were significantly associated with short term survival in malignant astrocytomas (n = 97, p = 0.016). In human brain tumor specimens, the production and phosphorylation of ephrin-B2 were high in GBM. Immunohistochemistry demonstrated ephrin-B2 localization primarily in GBM cells but not in normal brain. A highly invasive glioma cell line, U87, expressed high levels of ephrin-B2 compared with relatively less invasive cell lines. Treatment with EphB2/Fc chimera further enhanced migration and invasion of U87 cells, whereas treatment with an ephrin-B2 blocking antibody significantly slowed migration and invasion. Forced expression of ephrin-B2 in the U251 cell line stimulated migration and invasion in vitro and ex vivo, concomitant with tyrosine phosphorylation of ephrin-B2. These results demonstrate that high expression of ephrin-B2 is a strong predictor of short-term survival and that ephrin-B2 plays a critical role in glioma invasion rendering this signaling pathway as a potential therapeutic target.

A Case of Suprasellar Papillary Glioneuronal Tumor Mimicking Craniopharyngioma.

Papillary glioneuronal tumor (PGNT) is a low-grade biphasic neoplasm with astrocytic and neuronal differentiation. This tumor occurs most commonly in the frontal and temporal lobes, close to the ventricles, and rarely in the cerebellum, brainstem, and pineal gland. However, there has been no report of this tumor in the suprasellar region to date. In this paper, we report a case of PGNT in the suprasellar region in a 16-year-old girl. Magnetic resonance imaging (MRI) revealed a cystic tumor with calcification that progressed from the anterior skull base to the suprasellar and temporal regions. Preoperatively distinguishing this tumor from craniopharyngioma was difficult because of the patient's age, localization of the tumor, and neuroimaging results. This case showed a backward shift of the chiasma, which is observed in only 4.7% of craniopharyngioma, as well as normal endocrine findings. Endocrinological examination and an MRI evaluation of the chiasmal shift may be useful for discrimination.

A dedifferentiated intracranial solitary fibrous tumor with osteosarcoma components: rapid tumor progression and lethal clinical course.

Solitary fibrous tumor/hemangiopericytoma is a mesenchymal tumor that originates from a common NAB2-STAT6 fusion gene and is known to very rarely demonstrate dedifferentiation in the pattern of local recurrence or distant metastasis. Here we describe for the first time a rare case of intracranial dedifferentiated solitary fibrous tumor/hemangiopericytoma with osteosarcoma components that developed in an 84-year-old man after frequent gamma knife radiosurgery over a 14-year period. We performed tumor-debulking and gamma knife radiosurgery, but unfortunately the patient died shortly after the development of dedifferentiation. There is no established treatment for dedifferentiated cases due to the rare histology and limited published data, and therefore further accumulation of histological and genetic profiles is necessary to develop novel target gene therapies.

Intracytoplasmic Lumen in Urine Cytology Predicts Worse Prognosis in Non-Muscle-Invasive Bladder Cancers.

BACKGROUND: Intracytoplasmic lumina (ICL) are observed in several cancers, including urothelial carcinoma (UC). We have reported that ICL in urine cytology (cICL) is more frequent in high-grade UCs than in low-grade UCs; however, the correlation between the presence of ICL and prognosis is unclear. OBJECTIVES: The aim of this work was to determine the association between cICL and prognosis in bladder cancer. METHOD: We retrospectively investigated 87 patients with bladder cancer who received a histological diagnosis within 3 months of urine cytology at Kanazawa Medical University between 2003 and 2007. The cytological diagnosis and the number of cICL, histological diagnosis, tumor grade or variant, pT stage, ICL in histological specimens, and immunohistochemistry for mucins were evaluated. Data on the treatment type, recurrence, survival, cause of death, and length of follow-up were collected from electronic medical records. RESULTS: Muscle invasion, high-grade UC, lymph node metastasis, distant metastasis, adjuvant therapy, and disease-related mortality were more frequent in patients with cICL-positive bladder cancer than in those without cICL-positive bladder cancer. Immunohistochemistry revealed the expression of Muc-1 and Muc-4 in patients with cICL-positive bladder cancer. Univariate analysis revealed that cytological diagnosis by the Paris system and the 2015 version of the Japanese reporting system, muscle invasion, high-grade UC, lymph node metastasis, distant metastasis, and adjuvant chemotherapy and/or radiotherapy were significant factors associated with prognosis. Furthermore, survival was shorter in patients with cICL-positive non-muscle-invasive bladder cancer than in those with cICL-negative non-muscle-invasive bladder cancer. In the multivariate analysis, only distant metastasis was significantly associated with survival. CONCLUSIONS: cICL predicted shorter survival in patients with non-muscle-invasive bladder cancer, suggesting that ICL is one of the important diagnostic features of high-grade UC with a worse prognosis in urine cytology.

Telomere shortening in the damaged small bile ducts in primary biliary cirrhosis reflects ongoing cellular senescence.

UNLABELLED: Telomere shortening is a trigger of cellular senescence. Biliary epithelial cells in damaged small bile ducts in primary biliary cirrhosis (PBC) show senescent features such as the expression of senescence-associated beta-galactosidase and the increased expression of p16(INK4a) and p21(WAF1/Cip1). We investigated whether the telomere shortening is involved in the pathogenesis of biliary cellular senescence in PBC. We analyzed the telomere length of biliary epithelial cells using quantitative fluorescence in situ hybridization in livers taken from the patients with PBC (n = 13) and control livers (n = 13). We also assessed immunohistochemically the prevalence of DNA damage and the expression of p16(INK4a) and p21(WAF1/Cip1). The study showed a significant decrease in telomere length in biliary epithelial cells in the damaged small bile ducts and bile ductules in PBC compared with normal-looking bile ducts and bile ductules in PBC, chronic viral hepatitis, and normal livers (P < 0.01). gammaH2AX-DNA-damage-foci were detected in biliary epithelial cells in damaged small bile ducts and bile ductules in PBC but were absent in biliary epithelial cells in chronic viral hepatitis and normal livers. The expression of p16(INK4a) and p21(WAF1/Cip1) was increased corresponding to telomere shortening and gammaH2AX-DNA-damage-foci in the damaged small bile ducts in PBC. CONCLUSION: Telomere shortening and an accumulation of DNA damage coincide with increased expression of p16(INK4a) and p21(WAF1/Cip1) in the damaged bile ducts, characterize biliary cellular senescence, and may play a role in the following progressive bile duct loss in PBC.

Pituitary macroadenoma: Accuracy of apparent diffusion coefficient magnetic resonance imaging in grading tumor aggressiveness.

PURPOSE: The purpose of this study is to evaluate the accuracy of apparent diffusion coefficient magnetic resonance imaging in grading tumor aggressiveness using histogram apparent diffusion coefficient values. MATERIALS AND METHODS: Eighteen patients with surgically proved pituitary macroadenomas were included in this study. Diffusion-weighted imaging with single-shot echo-planar sequence at 3-T with a 32-channel head coil was performed with b values of 0 and 1000 s/mm2. Calculated apparent diffusion coefficient maps were generated, and a 3-D volume of interest was placed on the tumor while superimposing contrast-enhanced magnetic resonance images. All apparent diffusion coefficient values within the volume of interest were used to compute the average apparent diffusion coefficient of the tumor. The apparent diffusion coefficient values were binned to construct the apparent diffusion coefficient histogram. Using the histogram, the mean, percentiles, skewness, and kurtosis of the apparent diffusion coefficient of the entire tumor were computed. Apparent diffusion coefficient histogram parameters were compared with the MIB-1 index, invasiveness, and recurrence for grading tumor aggressiveness of pituitary adenomas. RESULTS: The skewness of the apparent diffusion coefficient histogram only showed significant differences among MIB-1 indices ( p = 0.030). All apparent diffusion coefficient histogram parameters showed no significant differences between negative and positive invasion. The skewness and kurtosis of the apparent diffusion coefficient histogram showed significant differences between positive and negative recurrence (skewness p = 0.011, kurtosis p = 0.011). Receiver-operating characteristics analysis between positive and negative recurrence showed that both skewness and kurtosis of the apparent diffusion coefficient achieved area under the curve at 0.967. CONCLUSION: Skewness and kurtosis of the apparent diffusion coefficient histogram were the predictive parameters for assessing tumor proliferative potential and recurrence of pituitary adenomas.

The clinicopathological analysis of receptor tyrosine kinases in meningiomas: the expression of VEGFR-2 in meningioma was associated with a higher WHO grade and shorter progression-free survival.

WHO grade II/III meningiomas recur frequently and there is currently no established molecular target therapy for meningioma. No previous studies have revealed the association between receptor tyrosine kinases (RTKs) and the recurrence of meningiomas. This study aims to elucidate the association between RTKs and the clinicopathological characteristics and recurrence of meningioma. We investigated the immunohistochemical expression of RTKs (VEGFR-1/2/3, PDGFR-alpha/beta and c-Kit) in 81 meningiomas (WHO grade I, n = 64, WHO grade II/III, n = 17) in 74 patients. Immunohistochemistry revealed that 29 WHO grade I (45%), 10 WHO grade II (77%), and 4 WHO grade III (100%) tumors were VEGFR-2-positive, and that the VEGFR-2 expression was significantly correlated with the WHO grade. In univariate analyses to investigate the clinicopathological factors associated with recurrence, Simpson grade IV/V resection, a larger tumor size, a high VEGFR-2 expression level, WHO grade II/III, a high Ki-67 expression level, and the non-expression of PgR were identified as significant factors. Furthermore, patients with VEGFR-2-positive meningiomas showed significantly shorter progression-free survival. In the multivariate analysis, WHO grade II/III and the location were significantly associated with recurrence. In conclusion, our study suggests that VEGFR-2 inhibitors might be one of the best candidates for molecular therapy against recurrent meningiomas.