Oligodendroglioma, IDH-mutant and 1p/19q-codeleted-prognostic factors, standard of care and chemotherapy, and future perspectives with neoadjuvant strategy.

Oligodendroglioma, IDH-mutant and 1p/19q-codeleted is known for their relative chemosensitivity and indolent clinical course among diffuse gliomas of adult type. Based on the data from phase 3 clinical trials, the standard of post-surgical care for those tumors is considered to be initial chemoradiotherapy regardless of histopathological grade, particularly with PCV. However, partly due to its renewed definition in late years, prognostic factors in patients with those tumors are not well established. Moreover, the survival rate declines over 15 years, with only a 37% OS rate at 20 years for grade 3 tumors, even with the current standard of care. Given that most of this disease occurs in young or middle-aged adults, further improvements in treatment and management are necessary. Here, we discuss prognostic factors, standard of care and chemotherapy, and future perspectives with neoadjuvant strategy in those tumors.

The Role of Genetic Analysis in Distinguishing Multifocal and Multicentric Glioblastomas: An Illustrative Case.

Introduction: Glioblastomas can manifest as multiple, simultaneous, noncontiguous lesions. We genetically analyzed multiple glioblastomas and discuss their etiological origins in this report. Case Presentation: We present the case of a 47-year-old woman who presented with memory impairment and left partial paralysis. Radiographic imaging revealed three apparently noncontiguous lesions in the right temporal and parietal lobes extending into the corpus callosum, leading to diagnosis of multicentric glioblastomas. All three lesions were excised. Genetic analysis of the lesions revealed a TERT promoter C228T mutation, a roughly equivalent amplification of EGFR, and homozygous deletion of CDKN2A/B exclusively in the two contrast-enhanced lesions. Additionally, the contrast-enhanced lesions exhibited the same two-base pair mutations of PTEN, whereas the non-enhanced lesion showed a partially distinct 13-base pair mutation. The other genetic characteristics were consistent. Rather than each having arisen de novo, we believe that they had developed by infiltration and are therefore best classified as multifocal glioblastomas. Conclusion: Our findings underscore anew the possibility of infiltration by glioblastomas, even within regions devoid of signal alterations on T2-weighted images or fluid-attenuated inversion recovery images. Genetic analysis can play a crucial role in differentiating whether multiple glioblastomas are multifocal or multicentric.

Fate and Efficacy of Engineered Allogeneic Stem Cells Targeting Cell Death and Proliferation Pathways in Primary and Brain Metastatic Lung Cancer.

Primary and metastatic lung cancer is a leading cause of cancer-related death and novel therapies are urgently needed. Epidermal growth factor receptor (EGFR) and death receptor (DR) 4/5 are both highly expressed in primary and metastatic non-small cell lung cancer (NSCLC); however, targeting these receptors individually has demonstrated limited therapeutic benefit in patients. In this study, we created and characterized diagnostic and therapeutic stem cells (SC), expressing EGFR-targeted nanobody (EV) fused to the extracellular domain of death DR4/5 ligand (DRL) (EVDRL) that simultaneously targets EGFR and DR4/5, in primary and metastatic NSCLC tumor models. We show that EVDRL targets both cell surface receptors, and induces caspase-mediated apoptosis in a broad spectrum of NSCLC cell lines. Utilizing real-time dual imaging and correlative immunohistochemistry, we show that allogeneic SCs home to tumors and when engineered to express EVDRL, alleviate tumor burden and significantly increase survival in primary and brain metastatic NSCLC. This study reports mechanistic insights into simultaneous targeting of EGFR- and DR4/5 in lung tumors and presents a promising approach for translation into the clinical setting.

[Medical Treatments for Malignant Brain Tumor].

Treatment of brain tumors, particularly malignant gliomas, is challenging using only surgical resection and radiation therapy, and medical treatment plays an important role in the management of these malignancies. Temozolomide has been mainly used for the treatment of malignant gliomas over a decade. However, novel therapeutic options, such as molecular-targeted drugs and oncolytic virus therapeutic agents have been introduced in recent years. Classical anticancer medications, such as nitrosoureas and platinum-based drugs, continue to be administered for treatment of some types of malignant brain tumors.

Gene-edited and -engineered stem cell platform drives immunotherapy for brain metastatic melanomas.

Oncolytic virus therapy has shown activity against primary melanomas; however, its efficacy in brain metastases remains challenging, mainly because of the delivery and immunosuppressive nature of tumors in the brain. To address this challenge, we first established PTEN-deficient melanoma brain metastasis mouse models and characterized them to be more immunosuppressive compared with primary melanoma, mimicking the clinical settings. Next, we developed an allogeneic twin stem cell (TSC) system composed of two tumor-targeting stem cell (SC) populations. One SC was loaded with oncolytic herpes simplex virus (oHSV), and the other SC was CRISPR-Cas9 gene-edited to knock out nectin 1 (N1) receptor (N1KO) to acquire resistance to oHSV and release immunomodulators, such as granulocyte-macrophage colony-stimulating factor (GM-CSF). Using mouse models of brain metastatic BRAFV600E/PTEN-/- and BRAFV600E/wt/PTEN-/- mutant melanomas, we show that locoregional delivery of TSCs releasing oHSV and GM-CSF (TSC-G) activated dendritic cell- and T cell-mediated immune responses. In addition, our strategy exhibited greater therapeutic efficacy when compared with the existing oncolytic viral therapeutic approaches. Moreover, the TSCs composed of SC-oHSV and SCN1KO-releasing GM-CSF and single-chain variable fragment anti-PD-1 (TSC-G/P) had therapeutic efficacy in both syngeneic and patient-derived humanized mouse models of leptomeningeal metastasis. Our findings provide a promising allogeneic SC-based immunotherapeutic strategy against melanomas in the CNS and a road map toward clinical translation.

Volumetric measurement of paranasal sinuses and its clinical significance in pituitary neuroendocrine tumors operated using an endoscopic endonasal approach.

Objective: Endoscopic endonasal surgery (EES) for deep intracranial lesions has gained popularity following recent developments in endoscopic technology. The operability of invasive pituitary neuroendocrine tumors (PitNETs) depends on the anatomy of the nasal cavity and paranasal sinus. This study aimed to establish a simple volume reconstruction algorithm of the nasal cavity and paranasal sinus. Additionally, this is the first study to demonstrate the relationship between the segmentation method and the clinical significance in patients with PitNET. Methods: Pre-and postoperative tumor volumes were analyzed in 106 patients with primary (new-onset) PitNETs (80 nonfunctioning and 26 functioning) who underwent EES. The efficiency and accuracy of the semiautomatic segmentation with manual adjustments (SSMA) method was compared with other established segmentation methods for volumetric analysis in the nasal cavity and paranasal sinuses. Correlations between the measured nasal cavity and paranasal sinus volumes and the extent of tumor removal were evaluated. Results: The SSMA method yielded accurate and time-saving results following the volumetric analyses of nasal cavity and paranasal sinuses with complex structures. Alternatively, the manual and semiautomatic segmentation methods proved time-consuming and inaccurate, respectively. The sphenoid sinus volume measured by SSMA was significantly correlated with the extent of tumor removal in patients with nonfunctioning Knosp grade 3 and 4 PitNET (r = 0.318; p = 0.015). Conclusion: The volume of sphenoid sinus potentially could predict the extent of resection due to better visualization of the tumor for PitNETs with CS invasion.

Surgical risk assessment for super-elderly patients.

AIM: Super-elderly patients are often frail and the decision on surgical indications remains a difficult issue. The purpose of this study was to provide a certain preoperative surgical risk assessment tool for super-elderly people. METHODS: We selected 112 individuals who were super-elderly patients aged >90 years who had surgeries under general anesthesia in our department. Based on the quality of the postoperative outcome of each case, we categorized these patients into two groups: good and poor groups. We evaluated the fundamental examination items, such as American Society of Anesthesiologists physical status, skeletal muscle mass index and so on, and a couple of the well-known risk score systems represented by Estimation of Physiology Ability and Surgical Stress. RESULTS: A total of 85 of the 112 patients belonged to the good group and the rest belonged to the poor group. The quality of postoperative outcome is well characterized by Estimation of Physiology Ability and Surgical Stress (P = 0.001). Receiver operating characteristic analysis of Estimation of Physiology Ability and Surgical Stress for the quality of postoperative outcome shows sensitivity of 0.83 and specificity of 0.61. Multivariate logistic regression analysis showed that skeletal muscle mass index and American Society of Anesthesiologists physical status are prominent as the risk determinants affecting the quality of postoperative outcome. A scoring system based on the skeletal muscle mass index, which is a good index of sarcopenia, and American Society of Anesthesiologists physical status, named the "SAP score" has the following characteristics. P-value <0.001, sensitivity 0.76 and specificity 0.91. CONCLUSIONS: Informed consent based on the risk score might be able to reduce the regrettable situation where it would have been better to have had surgery or not to have had surgery. Geriatr Gerontol Int 2022; 22: 271-277.

Histopathological investigation of the 1p/19q-codeleted gliomas resected following alkylating agent chemotherapy.

PURPOSE: Lower grade gliomas with 1p/19q codeletion are often responsive to chemotherapy, and several of these have been treated using upfront chemotherapy and subsequent resection following tumor volume decrease. This study aimed to elucidate the histological changes and the mechanism of recurrence after alkylating agent chemotherapy in 1p/19-codeleted gliomas. METHODS: Fourteen 1p/19q-codeleted gliomas resected following tumor volume decrease after alkylating agent chemotherapy were included and compared with their pre-chemotherapy specimens. Histological changes were investigated using hematoxylin-eosin staining, and changes in proliferative activity, status of glioma stem cells (GSCs), and tumor-infiltrating macrophages were assessed using immunohistochemistry for Ki-67/MIB-1, CD68 as a pan-macrophage/monocyte marker, CD163 as a presumed marker of M2 polarity, and nestin and CD133 as markers of GSCs. RESULTS: The most frequent histological findings following chemotherapy included a sparse glial background and abundant foamy cell infiltration. The Ki-67/MIB-1 index decreased and the number of CD68 + cells increased after chemotherapy. The increasing rate of CD68 + cells in the post-/pre-chemotherapy specimens was inversely correlated with patient prognosis but not tumor response. The number of CD163 + cells, M2/M1 + M2 ratio, and the ratio of GSCs to total tumor cells increased after chemotherapy, and those in the post-chemotherapy specimens were negatively correlated with patient prognosis. There was a correlation between the M2/M1 + M2 ratio and the ratio of GSCs in both pre- and post-chemotherapy specimens. CONCLUSION: GSCs in conjunction with M2 macrophages constitute the mechanism of resistance to and recurrence after alkylating agent chemotherapy in 1p/19q-codeleted gliomas.

Molecular investigation of brain tumors progressing during pregnancy or postpartum period: the association between tumor type, their receptors, and the timing of presentation.

OBJECTIVE: Brain tumors often become clinically evident during pregnancy; however, the mechanism has not been well elucidated. Purpose of this study is to investigate the influence of molecular genetic factors on the progression of brain tumors during pregnancy or the postpartum period. METHODS: Twelve cases of brain tumors that presented during pregnancy or postpartum period were included: five gliomas, three meningiomas, two vestibular schwannomas, and two chordomas. Tumor samples were investigated by metaphase comparative genomic hybridization and immunohistochemistry, for chromosomal copy number aberration (CNA) and receptor expression of sex hormones and growth factors. RESULTS: The results were correlated with the timing of tumor presentation in relation to the stage of pregnancy. EGFR, VEGFR-1/2, AR, and c-Myc were expressed in gliomas, PgR, ER, HER-2, VEGFR-1, EGF and VEGFR2 in meningiomas, VEGFR-1 in vestibular schwannomas, and EGFR, VEGFR-1/2, and c-Myc in chordomas. The CNAs of the tumors varied. Four of the five gliomas presented in the 2nd trimester, all three meningiomas in the 3rd trimester or postpartum period, and both of the two schwannomas in the late 2nd trimester. Expression of VEGFR-1/2 and EGFR was observed regardless of the timing of tumor presentation, whereas female hormone receptors and HER-2 were exclusively found in meningiomas. Interestingly, one anaplastic astrocytoma (IDH mut, non-codeleted) that progressed from precedent grade 2 tumor harbored amplification of the MYC locus. CONCLUSION: Progression of brain tumors during pregnancy is associated with various growth factors as well as sex hormones. The timing of presentation is likely dependent on molecular receptors specific to each tumor type.

Anti-EGFR VHH-armed death receptor ligand-engineered allogeneic stem cells have therapeutic efficacy in diverse brain metastatic breast cancers.

Basal-like breast cancer (BLBC) shows brain metastatic (BM) capability and overexpresses EGFR and death-receptors 4/5 (DR4/5); however, the anatomical location of BM prohibits efficient drug-delivery to these targetable markers. In this study, we developed BLBC-BM mouse models featuring different patterns of BMs and explored the versatility of estem cell (SC)-mediated bi-functional EGFR and DR4/5-targeted treatment in these models. Most BLBC lines demonstrated a high sensitivity to EGFR and DR4/5 bi-targeting therapeutic protein, EVDRL [anti-EGFR VHH (EV) fused to DR ligand (DRL)]. Functional analyses using inhibitors and CRISPR-Cas9 knockouts revealed that the EV domain facilitated in augmenting DR4/5-DRL binding and enhancing DRL-induced apoptosis. EVDRL secreting stem cells alleviated tumor-burden and significantly increased survival in mouse models of residual-tumor after macrometastasis resection, perivascular niche micrometastasis, and leptomeningeal metastasis. This study reports mechanism based simultaneous targeting of EGFR and DR4/5 in BLBC and defines a new treatment paradigm for treatment of BM.

Next-generation immunotherapies for brain metastatic cancers.

Patients with extracranial tumors, like lung, breast, and skin cancers, often develop brain metastases (BM) during the course of their diseases and BM commonly represent the terminal stage of cancer progression. Recent insights in the immune biology of BM and the increasing focus of immunotherapy as a therapeutic option for cancer has prompted testing of promising biological immunotherapies, including immune cell-targeting, virotherapy, vaccines, and different cell-based therapies. Here, we review the pathobiology of BM progression and evaluate the potential of next-generation immunotherapies for BM tumors. We also provide future perspectives on the development and implementation of such therapies for brain metastatic cancer patients.

A retrospective analysis of treatment outcomes in 45 patients with cardiac light-chain amyloidosis: a single-center experience in Japan.

The prognosis of cardiac light-chain (AL) amyloidosis is considered to be very poor. We studied the treatment efficacy and outcomes by retrospectively analyzing the clinical results of 45 patients with cardiac AL amyloidosis treated at our hospital between September 2008 and March 2016. The group of patients analyzed included 29 males and 16 females with a median age of 68 years. Their baseline median NT-proBNP, cTnT, and dFLC were 3167 pg/ml, 0.080 ng/ml, and 286.17 mg/l, respectively. Twenty-eight patients were in Cardiac Stage (CS) III and 17 patients were in Revised Prognostic Stage (RPS) IV. At the median follow-up of 10 months, the median overall survival (OS) was 16 months and 3-year OS was 35.9%. The patients in CS III showed significantly poorer survival rate than those in CS I or II (3-year OS: 12.2% vs. 65.8%, p = 0.0115) and the patients in RPS IV showed significantly poorer survival rate than those in RPS I, II, or III (3-year OS: 11.0% vs. 53.3%, p = 0.000914). Regardless of the therapeutic approaches, patients who achieved hematological CR or cardiac organ response demonstrated significantly improved prognosis. Therefore, achievement of hematological and organ responses is important in the treatment of cardiac AL amyloidosis.

Umbilical cord blood stearoyl-CoA desaturase index and lipoprotein lipase mass level in small-for-gestational age newborns.

We previously reported that triglyceride (TG) levels in small-for-gestational age (SGA) newborns were significantly higher than those in appropriate-for-gestational age (AGA) newborns. Stearoyl-CoA desaturase (SCD) activity is required for TG synthesis, while lipoprotein lipase mass (LPLm) facilitates TG clearance. The purpose of this study is to reveal whether SCD activity or LPLm is the cause of high TG levels in SGA newborns. Fifty-five newborns were classified as AGA (n = 42) and SGA (n = 13). Serum LPLm, TG and fatty acids in umbilical cord blood were analyzed. Then, [16:1 (n-7)]/ [16:0] and [18:1 (n-9)]/ [18:0] were calculated as SCD16 and SCD18 activities, respectively. The SGA group showed significantly higher TG levels and significantly lower LPLm levels than the AGA group. However, SCD16 and 18 activities were lower in SGA newborns than in AGA newborns. In conclusion, LPLm, rather than SCD activity may be involved in the increased TG levels in SGA newborns.

Plasma Albumin Redox State Is Responsive to the Amino Acid Balance of Dietary Proteins in Rats Fed a Low Protein Diet.

We recently reported that plasma albumin redox state, which correlates with albumin synthesis rate, could be associated with the quality of dietary protein. Aiming to elucidate the association between them, plasma albumin redox state was investigated in rats fed various kinds of AIN-93G-based low protein diets. Plasma albumin redox state was shifted to a more oxidized state in rats fed 3% casein (CN) diet than those fed 3% whey protein or 3% wheat gluten diet, while supplementing 3% CN diet with cystine reversed it to a more reduced state, indicating that cystine would complement the shortage of cysteine in CN, thereby increasing albumin synthesis rate. Supplementation with glutathione, a cysteine-containing antioxidative tripeptide, normalized hepatic glutathione redox state modulated by ingestion of 3% CN diet, but it only reversed the oxidized shift of plasma albumin redox state to an extent similar to cystine alone or the constituting amino acid mixture of glutathione (i.e., glutamic acid, cystine, and glycine), indicating that glutathione would primarily serve as a source of cysteine rather than exert its antioxidative activity. Plasma albumin would thus be influenced by amino acid balance in dietary proteins, and it could be useful as a biomarker that contributes to prevention of protein under-nutriton, caused by not only insufficient protein intake but also ingestion of poor-quality protein.

Fatty Acid Composition of the Erythrocyte Membranes Varies between Early-Term, Full-Term, and Late-Term Infants in Japan.

BACKGROUND: Term infants can be categorized into 3 sub-groups: early term (37w0d to 38w6d), full term (39w0d to 40w6d), and late term (41w0d and beyond). However, the fatty acid composition among the 3 groups of term infants has not been investigated. The association between fatty acid composition and gestational period of term infants in Japan is unclear. METHODS: We assessed the fatty acid composition of maternal erythrocyte membranes in the third trimester and of cord erythrocyte membranes at birth in 212 healthy term Japanese infants using data from a prospective hospital-based cohort study. RESULTS: In maternal erythrocyte membranes, docosahexaenoic acid (DHA) levels and omega-3 index were significantly higher in the late-term group than in the early-term group. In cord erythrocyte membranes, DHA levels were not significantly different between the 3 groups; late-term infants showed significantly higher DHA/arachidonic acid (ARA) and lower 20: 3n-6 and ARA levels compared to early-term infants. Gestational period positively correlated with the DHA status in maternal and cord erythrocyte membranes. CONCLUSIONS: Fatty acid composition in maternal and cord erythrocyte membranes varies between early-, full-, and late-term infants, and the greater gestational period may contribute to the relatively high n-3 polyunsaturated fatty acids status in term infants. Furthermore, maternal DHA status in the third semester directly correlates with gestational period in pregnant Japanese women.

Association between programmed cell death ligand-1 expression and extracranial metastasis in intracranial solitary fibrous tumor/hemangiopericytoma.

BACKGROUND: Intracranial solitary fibrous tumor/hemangiopericytoma (SFT/HPC) often shows extracranial metastasis, and treatment options are very limited. Immune-checkpoint molecules have not been studied well in SFT/HPCs, and their role in intracranial SFT/HPCs remains unclear. METHODS: We investigated the expression of programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), and tumor-infiltrating lymphocytes (TIL) in 16 patients of intracranial SFT/HPC by immunohistochemistry to determine if correlation with prognosis exists. RESULTS: Median overall survival (OS) of 16 patients was 9.2 years, and median follow-up of alive patients was 9.9 years. Recurrence was observed in 13 (81.3%) patients, and extracranial metastasis were observed in 6 (37.5%). PD-L1 expression was observed in all 16 tumors, whereas PD-1 expression was observed in 2. CD3 and CD8 expressions were observed in TILs in 12 and 13 patients respectively. Although the ratio of PD-L1 positive-tumor cells was not associated with OS, progression-free survival, or metastasis-free survival (MFS), diffuse staining of PD-L1 showed a trend toward shorter time to treatment failure (TTF: time to either extracranial metastasis or death) (p = 0.072). Similarly, the intense staining of PD-L1 was associated with shorter MFS (p = 0.0084) and TTF (p = 0.033). CD3 or CD8 expression was not associated with any of the prognostic parameters. In the combined analysis of PD-L1 and CD8, diffuse PD-L1 staining coupled with no or sparse CD8 expression was significantly associated with a shorter TTF (p = 0.005) and showed a trend toward shorter MFS (p = 0.0611). CONCLUSIONS: PD-L1 is frequently expressed in intracranial SFT/HPCs, and diffuse or intense PD-L1 expression might be associated with the early occurrence of extracranial metastases.

Epigenetic modulation of Fgf21 in the perinatal mouse liver ameliorates diet-induced obesity in adulthood.

The nutritional environment to which animals are exposed in early life can lead to epigenetic changes in the genome that influence the risk of obesity in later life. Here, we demonstrate that the fibroblast growth factor-21 gene (Fgf21) is subject to peroxisome proliferator-activated receptor (PPAR) α-dependent DNA demethylation in the liver during the postnatal period. Reductions in Fgf21 methylation can be enhanced via pharmacologic activation of PPARα during the suckling period. We also reveal that the DNA methylation status of Fgf21, once established in early life, is relatively stable and persists into adulthood. Reduced DNA methylation is associated with enhanced induction of hepatic FGF21 expression after PPARα activation, which may partly explain the attenuation of diet-induced obesity in adulthood. We propose that Fgf21 methylation represents a form of epigenetic memory that persists into adulthood, and it may have a role in the developmental programming of obesity.

Comprehensive genetic characterization of rosette-forming glioneuronal tumors: independent component analysis by tissue microdissection.

A rosette-forming glioneuronal tumor (RGNT) is a rare mixed neuronal-glial tumor characterized by biphasic architecture of glial and neurocytic components. The number of reports of genetic analyses of RGNTs is few. Additionally, the genetic background of the unique biphasic pathological characteristics of such mixed neuronal-glial tumors remains unclear. To clarify the genetic background of RGNTs, we performed separate comprehensive genetic analyses of glial and neurocytic components of five RGNTs, by tissue microdissection. Two missense mutations in FGFR1 in both components of two cases, and one mutation in PIK3CA in both components of one case, were detected. In the latter case with PIK3CA mutation, the additional FGFR1 mutation was detected only in the glial component. Moreover, the loss of chromosome 13q in only the neurocytic component was observed in one other case. Their results suggested that RGNTs, which are tumors harboring two divergent differentiations that arose from a single clone, have a diverse genetic background. Although previous studies have suggested that RGNTs and pilocytic astrocytomas (PAs) represent the same tumor entity, their results confirm that the genetic background of RGNTs is not identical to that of PA.

Relationship between Changes in Fatty Acid Composition of the Erythrocyte Membranes and Fatty Acid Intake during Pregnancy in Pregnant Japanese Women.

OBJECTIVE: Docosahexaenoic acid (DHA) is an important nutrient required by pregnant women and fetuses. Several studies suggest that fatty acid composition changes during pregnancy. However, the association of longitudinal changes in erythrocyte fatty acid composition and dietary fatty acid intake during pregnancy is not well understood. We assessed the relationship between fatty acid composition of the erythrocyte membranes and fatty acid intake at each trimester in pregnant Japanese women. METHODS: We conducted a prospective hospital-based cohort study. We investigated fatty acid composition of the erythrocyte membranes and intake of fatty acids during the three trimesters in 178 healthy, pregnant Japanese women. RESULTS: The eicosapentaenoic acid and arachidonic acid percentage of the erythrocyte membranes significantly decreased. The percentages of linoleic acid and α-linolenic acid significantly increased during pregnancy. The DHA percentage in the erythrocyte membranes decreased from the second to the third trimester. The DHA percentage in the erythrocyte membranes positively correlated with DHA intake in the third trimester. CONCLUSION: In pregnant Japanese women, the fatty acid composition of the erythrocyte membranes markedly changed throughout pregnancy. The DHA intake in the third trimester may be insufficient to maintain DHA percentage in the maternal erythrocyte membranes.

Genetic aberrations and molecular biology of skull base chordoma and chondrosarcoma.

Chordomas and chondrosarcomas are two major malignant bone neoplasms located at the skull base. These tumors are rarely metastatic, but can be locally invasive and resistant to conventional chemotherapies and radiotherapies. Accordingly, therapeutic approaches for the treatment of these tumors can be difficult. Additionally, their location at the skull base makes them problematic. Although accurate diagnosis of these tumors is important because of their distinct prognoses, distinguishing between these tumor types is difficult due to overlapping radiological and histopathological findings. However, recent accumulation of molecular and genetic studies, including extracranial location analysis, has provided us clues for accurate diagnosis. In this report, we review the genetic aberrations and molecular biology of these two tumor types. Among the abundant genetic features of these tumors, brachyury immunohistochemistry and direct sequencing of IDH1/2 are simple and useful techniques that can be used to distinguish between these tumors. Although it is still unclear why these tumors, which have such distinct genetic backgrounds, show similar histopathological findings, comparison of their genetic backgrounds could provide essential information.