Growth risk classification and typical growth speed of convexity, parasagittal, and falx meningiomas: a retrospective cohort study.

OBJECTIVE: Meningiomas are the most common primary intracranial tumors, and their clinical and biological characteristics vary by location. Convexity, parasagittal, and falx meningiomas account for approximately 50%-65% of intracranial meningiomas. Focusing only on these locations, the aim of this study was to determine the typical speed of tumor growth, to assess the growth risk, and to show the possible tumor volume that many lesions can reach after 5 years. METHODS: Patients with radiologically suspected convexity, parasagittal, or falx meningiomas at the authors' institution were studied retrospectively. The relative growth rate (RGR) and annual volume change (AVC) were calculated from MRI at more than 3-month intervals. Based on sex, age, and signal intensity on T2-weighted MRI, the cases were classified into three groups: extremely high-growth, high-growth, and low-growth groups. RESULTS: The data of 313 cases were analyzed. The median RGR and AVC for this entire cohort were 6.1% (interquartile range [IQR] 2.4%-16.0%) and 0.20 (IQR 0.04-1.18) cm3/year, respectively. There were significant differences in sex (p = 0.018) and T2-weighted MRI signal intensity (p < 0.001) for RGR, and T2-weighted MRI signal intensity (p < 0.001), tumor location (p = 0.025), and initial tumor volume (p < 0.001) for AVC. The median RGR and AVC were 17.5% (IQR 8.3%-44.1%) and 1.05 (IQR 0.18-3.53) cm3/year, 8.2% (IQR 2.9%-18.6%) and 0.33 (IQR 0.06-1.66) cm3/year, and 3.4% (IQR 1.2%-5.8%) and 0.04 (IQR 0.02-0.21) cm3/year for the extremely high-growth, high-growth, and low-growth groups, respectively, with a significant difference among the groups (p < 0.001). A 2.24-times, or 5.24 cm3, increase in tumor volume over 5 years was typical in the extremely high-growth group, whereas the low-growth group showed little change in tumor volume even over a 5-year follow-up period. CONCLUSIONS: For the first time, the typical speed of tumor growth was calculated, focusing only on patients with convexity, parasagittal, and falx meningiomas. In addition, the possible tumor volume that many lesions in these locations can reach after 5 years was shown based on objective indicators. These results may allow clinicians to easily detect lesions that require frequent follow-up or early treatment by determining whether they deviate from the typical range of the growth rate, similar to a growth chart for children.

Identification of glioblastoma-specific antigens expressed in patient-derived tumor cells as candidate targets for chimeric antigen receptor T cell therapy.

Background: New therapies for glioblastoma (GBM) are urgently needed because the disease prognosis is poor. Chimeric antigen receptor (CAR)-T cell therapy that targets GBM-specific cell surface antigens is a promising therapeutic strategy. However, extensive transcriptome analyses have uncovered few GBM-specific target antigens. Methods: We established a library of monoclonal antibodies (mAbs) against a tumor cell line derived from a patient with GBM. We identified mAbs that reacted with tumor cell lines from patients with GBM but not with nonmalignant human brain cells. We then detected the antigens they recognized using expression cloning. CAR-T cells derived from a candidate mAb were generated and tested in vitro and in vivo. Results: We detected 507 mAbs that bound to tumor cell lines from patients with GBM. Among them, E61 and A13 reacted with tumor cell lines from most patients with GBM, but not with nonmalignant human brain cells. We found that B7-H3 was the antigen recognized but E61. CAR-T cells were established using the antigen-recognition domain of E61-secreted cytokines and exerted cytotoxicity in co-culture with tumor cells from patients with GBM. Conclusions: Cancer-specific targets for CAR-T cells were identified using a mAb library raised against primary GBM tumor cells from a patient. We identified a GBM-specific mAb and its antigen. More mAbs against various GBM samples and novel target antigens are expected to be identified using this strategy.

Revisiting the definition of glioma recurrence based on a phylogenetic investigation of primary and re-emerging tumor samples: a case report.

A recurrent tumor is defined as a re-emerging subclone originating from an ancestorial clone of the primary neoplasm. Hence, it should be distinguished from de novo tumor emerging from other clones. Herein, we describe an exceptional case in which the locally re-emerging glioma did not share genetic alterations of the primary tumor. While the initial tumor harbored mutations in IDH1 and TERT genes as well as 1p/19q codeletion, the re-emerging tumor did not present any of these genetic abnormalities. Variant calling for tumor samples using whole-genome sequencing revealed that 1696 mutations within the primary tumor faded in the re-emerging tumor, and that 4591 mutations were newly detected in the re-emerging tumor. These results suggested that the initial and re-emerging tumors did not share same clonal origins, although the second tumor appeared adjacent to the old surgical cavity 5 years after the initial surgery. We finally speculated that the re-emerging tumor could be a "de novo glioma" or "radiation-induced glioblastoma following treatment of a diffuse glioma." This case highlights the importance of molecular re-evaluation of clinically diagnosed "recurrent" glioma lesions.

Selective targeting of multiple myeloma cells with a monoclonal antibody recognizing the ubiquitous protein CD98 heavy chain.

Cancer-specific cell surface antigens are ideal therapeutic targets for monoclonal antibody (mAb)-based therapy. Here, we report that multiple myeloma (MM), an incurable hematological malignancy, can be specifically targeted by an mAb that recognizes a ubiquitously present protein, CD98 heavy chain (hc) (also known as SLC3A2). We screened more than 10,000 mAb clones raised against MM cells and identified R8H283, an mAb that bound MM cells but not normal hematopoietic or nonhematopoietic cells. R8H283 specifically recognized CD98hc. R8H283 did not react with monomers of CD98hc; instead, it bound CD98hc in heterodimers with a CD98 light chain (CD98lc), a complex that functions as an amino acid transporter. CD98 heterodimers were abundant on MM cells and took up amino acids for constitutive production of immunoglobulin. Although CD98 heterodimers were also present on normal leukocytes, R8H283 did not react with them. The glycoforms of CD98hc present on normal leukocytes were distinct from those present on MM cells, which may explain the lack of R8H283 reactivity to normal leukocytes. R8H283 exerted anti-MM effects without damaging normal hematopoietic cells. These findings suggested that R8H283 is a candidate for mAb-based therapies for MM. In addition, our findings showed that a cancer-specific conformational epitope in a ubiquitous protein, which cannot be identified by transcriptome or proteome analyses, can be found by extensive screening of primary human tumor samples.

How Much Tumor Volume Is Responsible for Development of Clinical Symptoms in Patients With Convexity, Parasagittal, and Falx Meningiomas?

Purpose: Meningiomas are the most common primary intracranial neoplasms and clinical symptom appearance depends on their volume and location. This study aimed to identify factors that influence clinical symptoms and to determine a specific threshold tumor volume for the prediction of symptomatic progression in patients with convexity, parasagittal, and falx meningiomas. Materials and Methods: We retrospectively studied patients with radiologically suspected convexity, parasagittal, or falx meningiomas at our institution. Results: The data of three hundred thirty-three patients were analyzed. We further divided patients into two groups based on clinical symptoms: an asymptomatic group (250 cases) and a symptomatic group (83 cases). Univariate analysis revealed significant differences between the groups in terms of sex (p = 0.002), age at the time of volumetric analysis (p < 0.001), hyperintense lesions on T2-weighted images (p = 0.029), peritumoral edema (p < 0.001), maximum tumor diameter (p < 0.001), and tumor volume (p < 0.001). Further multivariate analysis revealed significant differences between the groups in terms of age at the time of volumetric analysis (p = 0.002), peritumoral edema (p < 0.001), and tumor volume (p < 0.001). The receiver operating characteristic curve revealed a threshold tumor volume of 21.1 ml for predicting whether a patient would develop symptoms (sensitivity 0.843, specificity 0.880, an area under the curve 0.919 [95% confidence interval: 0.887-0.951]). Conclusion: We identified factors predictive of clinical symptoms in patients with convexity, parasagittal, and falx meningiomas and determined the first-ever threshold tumor volume for predicting symptomatic progression in such patients.

The Impact of 5-Year Tumor Doubling Time to Predict the Subsequent Long-Term Natural History of Asymptomatic Meningiomas.

OBJECTIVE: Meningiomas are the most frequent primary brain tumors. The long-term natural history of asymptomatic meningiomas remains unclear and difficult to predict accurately, however. The purpose of this study was to determine the subsequent course of asymptomatic meningiomas preceded by 5 years of no treatment. METHODS: We retrospectively studied patients with radiologically suspected intracranial asymptomatic meningiomas preceded by 5 years of no treatment. We volumetrically measured the lesions' chronological changes during the initial 5 years to obtain the 5-year tumor doubling time (5y-TdT). RESULTS: A total of 201 cases met the inclusion criteria. They were further divided into 3 subgroups: those who remained asymptomatic (group A; 174 cases), those who developed neurological symptoms and underwent treatment (group B; 8 cases), and those who received intentional intervention for a preventative reason (group C; 19 cases). 5y-TdT of group B (median: 46.5 months) was significantly shorter than that of group A (median: 216.3 months) (P < 0.001). Progression-free survival (PFS) was significantly different between tumors that exhibited 5y-TdT ≥ 98.8 months and <98.8 months (P < 0.001). When we combined groups B and C and set the PFS endpoint as either disease progression or treatment, we found that more than 20% of patients would require treatment within 15 years. CONCLUSIONS: The present study revealed the subsequent course of asymptomatic meningiomas after 5 years of no treatment and demonstrated that 5y-TdT is useful to detect patients who may require treatment.

Successful neurosurgical separation of conjoined spinal cords in pygopagus twins: illustrative cases.

BACKGROUND: Conjoined twins represent a rare congenital malformation. Pygopagus twins are fused at the sacrum and perineum, with union of the spine. The authors report a successful separation of a unique case of pygopagus twins sharing a U-shaped spinal cord, which the authors identified through aberrant nerves by intraoperative physiological spinal root examination. OBSERVATIONS: The 6-month-old male pygopagus conjoined twins, who were diagnosed in the prenatal period, underwent separation. They had a single dural sac containing a U-shaped continuous spinal cord; their filum terminale appeared completely fused and the anatomical border of the spinal cord was not distinguishable. A triggered electromyogram (tEMG) was used on each nerve root to determine which belonged to one twin versus the other, to detect nerve cross, and to identify functional midline cleavage. Finally, the twins were separated after spinal division. Both twins recovered uneventfully with no lower limb neurological deficits or walking impairment for 16 months. LESSONS: Pygopagus twins with a conjoined spinal cord are very rare, but a good long-term functional prognosis can be expected with successful separation. Intraoperative tEMG is useful in spinal separation surgery for twins with a conjoined spinal cord.

Coil Embolization for a Cerebral Aneurysm in a Heart Transplantation Patient: A Case Report.

The number of heart transplantations performed in Japan has been continuously increasing. Here, we report the case of a patient with an unruptured cerebral artery aneurysm after undergoing heart transplantation and was treated using coil embolization. The patient was a 50-year-old woman who was positive for heparin-induced thrombocytopenia (HIT) antibodies and underwent heart transplantation for dilated cardiomyopathy. An unruptured middle cerebral artery aneurysm was treated with coil embolization using argatroban as a heparin substitute. The patient was discharged without any complications. Despite these patients with heart transplantation are characterized by high HIT antibodies rate and the need for immunosuppressive agents, they currently have an excellent prognosis, especially in Japan. Therefore, the knowledge of patient characteristics after heart transplantation is essential for ensuring that these patients receive the most appropriate treatment.

Surgical Treatment of Brain Metastasis of Extramammary Paget's Disease: A Case Report.

Extramammary Paget's disease (EMPD) is a rare form of neoplasm. Metastasis of EMPD to locations other than lymph nodes and intra-epithelial regions is rare; there are a limited number of case reports of metastases to the liver, lung, bone, and brain. We present a rare case of EMPD that metastasized to the brain and was treated with surgical resection. A 66-year-old man presented with a small palpable mass in the scrotum. After 5 years of observation, he was diagnosed with EMPD that metastasized to the lymph nodes and lung. Tumor resection and postoperative chemotherapy were performed. Six months after the last chemotherapy treatment, he presented with a right temporal lobe tumor and underwent surgical resection. Histopathological analysis revealed brain metastasis of EMPD. Three months after surgery, magnetic resonance imaging (MRI) showed local tumor recurrence, and intensity modulated radiation therapy (IMRT) (45 Gy/15 Fr) was performed. Although the metastatic brain tumor was well controlled, the primary tumor progressed. He was provided best supportive care and died 5 months after brain tumor resection. In this report, we present a rare case of brain metastasis of EMPD, treated with surgical resection, and histopathologically confirmed to be metastatic EMPD.

Widespread subdural metastasis from breast cancer progressing rapidly with cerebral herniation: A case report.

We herein present the case of a 49-year-old female patient presenting with nausea and headache. The patient's medical history included breast cancer with bone and lymph node metastasis. Computed tomography (CT) examination revealed a high-density lesion in the right subdural space, suggesting hematoma. During surgery planned for subdural hematoma drainage, an en plaque subdural yellowish-white tumor was identified, without hematoma. Histopathological examination revealed metastatic breast cancer. The patient was administered predonisolone and her neurological symptoms gradually recovered. However, 12 days after the first operation, the clinical course was complicated by vomiting and rapid loss of consciousness. Emergency CT revealed that the subdural tumor had enlarged and decompression was performed as life-saving surgery. However, the patient's condition progressively deteriorated and she finally succumbed to the disease 2 months after the second operation. The aim of this study was to present the case of a patient with a large en plaque subdural tumor mimicking subdural hematoma and causing rapid loss of consciousness and cerebral herniation.