Reliable detection of genetic alterations in cyst fluid DNA for the diagnosis of brain tumors.

PURPOSE: Liquid biopsy of cyst fluid in brain tumors has not been extensively studied to date. The present study was performed to see whether diagnostic genetic alterations found in brain tumor tissue DNA could also be detected in cell-free DNA (cfDNA) of cyst fluid in cystic brain tumors. METHODS: Cyst fluid was obtained from 22 patients undergoing surgery for a cystic brain tumor with confirmed genetic alterations in tumor DNA. Pathological diagnoses based on WHO 2021 classification and diagnostic alterations in the tumor DNA, such as IDH1 R132H and TERT promoter mutation for oligodendrogliomas, were detected by Sanger sequencing. The same alterations were analyzed by both droplet digital PCR (ddPCR) and Sanger sequencing in cyst fluid cfDNA. Additionally, multiplex ligation-dependent probe amplification (MLPA) assays were performed to assess 1p/19q status, presence of CDKN2A loss, PTEN loss and EGFR amplification, to assess whether differentiating between astrocytomas and oligodendrogliomas and grading is possible from cyst fluid cfDNA. RESULTS: Twenty-five genetic alterations were found in 22 tumor samples. All (100%) alterations were detected in cyst fluid cfDNA by ddPCR. Twenty of the 25 (80%) alterations were also detected by Sanger sequencing of cyst fluid cfDNA. Variant allele frequency (VAF) in cyst fluid cfDNA was comparable to that of tumor DNA (R = 0.62, Pearson's correlation). MLPA was feasible in 11 out of 17 (65%) diffuse gliomas, with close correlation of results between tumor DNA and cyst fluid cfDNA. CONCLUSION: Cell-free DNA obtained from cyst fluid in cystic brain tumors is a reliable alternative to tumor DNA when diagnosing brain tumors.

Neuropil-like islands are a possible pathogenetic link between glioblastoma and gangliocytoma/ganglioglioma in a case of synchronous bilateral brain tumors.

Neuropil-like islands (NIs) are a histologic hallmark of glioneuronal tumors with neuropil-like islands (GTNIs), but GTNIs are presently not considered a homogeneous entity. The essence of GTNI is likely its glial component, and NIs are now considered aberrant neuronal differentiation or metaplasia. The case we report herein is a 41-year-old woman who was synchronously affected by two brain tumors: one was a glioblastoma (glioblastoma multiforme, GBM), of isocitrate dehydrogenase (IDH)-wild type, with NIs in the left parietal lobe, and the other was histologically a composite gangliocytoma (GC)/anaplastic ganglioglioma (GG) with NIs in the right medial temporal lobe. While both tumors were genetically wild type for IDH, histone H3, and v-raf murine sarcoma viral oncogene homolog B1 (BRAF), the former tumor, but not the latter, was mutated for telomerase reverse transcriptase promoter gene (TERT). A recent systematic study using DNA methylation profiling and next-generation sequencing showed that anaplastic GG separate into other WHO tumor types, including IDH-wild-type GBM. It suggested a diagnostic scheme where an anaplastic GG is likely an IDH-wild-type GBM if it is a BRAF wild type, IDH wild type, and TERT promoter mutant tumor. The likely scenario in this patient is that the GBM results from the progression of GC/anaplastic GG due to the superimposed TERT promoter mutation and the propagation of newly generated GBM cells in the contralateral hemisphere. A systematic analysis using DNA methylation profiling and next-generation sequencing was not available in this study, but the common presence of NIs histologically noted in the two tumors could support this scenario. Although a sufficient volume of molecular and genetic testing is sine qua non for the accurate understanding of brain tumors, the importance of histologic observation cannot be overemphasized.

Miliary Tuberculosis during R-MPV Therapy in an Elderly Patient with Primary Central Nerve System Lymphoma: A Case Report.

Most elderly patients with tuberculosis (TB) have previously been infected with Mycobacterium tuberculosis, which remains dormant in the body for decades and may reactivate when their immunity declines due to underlying diseases. Elderly cancer patients are at a high risk for TB, and the treatment of TB reactivation in these patients is challenging. Among cancer patients, the incidence of TB reactivation is the highest in lymphoma patients. However, the impact of chemotherapy on TB reactivation in lymphoma patients is unknown. We report the case of an immunocompetent elderly patient with primary central nervous system lymphoma (PCNSL) having no prior history of TB, who developed miliary TB during multiagent chemotherapy consisting of rituximab, high-dose methotrexate, procarbazine, and vincristine (R-MPV therapy). Retrospectively, the chest computed tomography showed calcification of the pleura, suggesting that the patient had a latent tuberculosis infection (LTBI) and developed miliary TB from the reactivation of TB triggered by the R-MPV therapy. Our case emphasizes that when chemotherapy is administered to patients with PCNSL, interferon-gamma release assay (IGRA) should be performed if there are findings on chest examination suggestive of LTBI, such as pleural calcification, and if IGRA is positive, chemotherapy should be given concurrently with LTBI treatment.

Clinical significance and pitfalls of human chorionic gonadotropin-related tumor markers for intracranial germinomas.

PURPOSE: Measuring serum and cerebrospinal fluid human chorionic gonadotropin (hCG) is essential for the diagnosis of intracranial germ cell tumors. There are three types of hCG-related markers in clinical use: hCGß, intact hCG, and total hCG. The best marker for the diagnosis of intracranial germ cell tumors, especially germinoma, is currently unknown. This study aimed to evaluate the usefulness of these hCG-related markers. METHODS: We investigated 19 serum samples obtained from 6 patients with histologically diagnosed germinoma treated in our institute. Serum hCGß, intact hCG, and total hCG values were measured before, during, and after treatment. Samples with hCG values above the lower limits were considered positive. RESULTS: The positivity rates of serum hCGß, intact hCG, and total hCG were 6% (1/17), 47% (7/15), and 42% (8/19), respectively, with the latter two having significantly higher positivity rates than hCGß (p = 0.041). Both intact and total hCGs showed similar values. The median values of hCGß, intact hCG, and total hCG before treatment were 0.1 ng/mL, 4.6 mIU/mL, and 4.5 mIU/mL, respectively. CONCLUSION: Serum intact and total hCGs have higher detection rates than hCGß in patients with germinoma using available commercial measurement tools.

Successful Treatment of a CNS Tumor with BCOR Internal Tandem Duplication: A Case Report.

A central nervous system (CNS) tumor with BCL-6 co-repressor (BCOR) internal tandem duplication (CNS tumor with BCOR ITD) is a rare tumor classified as an embryonal tumor by the World Health Organization classification (5th edition), and the prognosis is generally poor. A successfully treated case is reported, and its treatment is discussed. A five-year-old boy presented with a one-month history of headache and vomiting. Magnetic resonance imaging showed a well-demarcated, left-frontal tumor without perifocal edema. The patient underwent complete resection without a neurological deficit. Anti-BCOR antibody showed strong immunoreactivity in tumor nuclei, and the tumor was diagnosed as a CNS tumor with BCOR ITD. The patient received craniospinal irradiation (CSI) comprising 23.4 Gy, followed by a boost to the primary site to a total dose of 30.6 Gy in daily fractions of 1.8 Gy. The chemotherapy comprised four cycles of vincristine, cyclophosphamide, and cisplatin with peripheral blood stem cell rescue. The clinical course was uneventful throughout the treatment, the tumor has not recurred for four years, and no neurological impairment was reported. CSI and multiagent chemotherapy were effective for a CNS tumor with BCOR ITD.

A case of aggressive pituitary neuroendocrine tumour with extremely rapid progression: possible diagnostic value of TERT promoter methylation.

Most pituitary adenoma/neuroendocrine tumours (PitNET) are histologically benign and grow slowly; however, a subset of these tumours exhibit a more aggressive clinical course characterized by local invasiveness and early recurrence. These high-risk PitNETs often require multiple surgeries and radiation over several years and may eventually acquire carcinomatous characteristics, such as metastasis in some cases. Herein, we report a rare case of PitNET causing oculomotor paresis with extremely rapid recurrence only 3 months after initial surgery, followed by lethal liver metastasis. Preoperative magnetic resonance imaging and intraoperative findings were consistent with typical PitNETs, other than moderate invasion of the cavernous sinus. Pathological examination of the specimen obtained from the initial transsphenoidal surgery revealed increased mitosis and elevated rates of cells positive for Ki-67 and p53. Based on the immunohistochemical assessment for transcription factors and pituitary hormones, the diagnosis was determined to be a silent sparsely granulated corticotroph PitNET with focal malignant transformation. Aggressive features represented by Ki-67 and p53 positivity were more robust in recurrent and metastatic specimens, but hormone immunostaining was decreased. Epigenetic analysis revealed methylation of the telomerase reverse transcriptase (TERT) promoter in the tumour, resulting in TERT upregulation. Despite extensive research, markers for distinguishing extremely aggressive PitNETs have not been determined. Although further analysis is needed, our case demonstrates the possible usefulness of assessing TERT promoter methylation status in the stratification of recurrence risk in extremely high-risk variants of PitNET.

Primary intramedullary spinal cord pilocytic astrocytoma with anaplasia in an adult: illustrative case.

BACKGROUND: Primary intramedullary spinal cord (IMSC) pilocytic astrocytoma (PA) with anaplasia is extremely rare. OBSERVATIONS: A 50-year-old man presented to our hospital with numbness of the left posterior rib region, back, and bilateral lower limbs. Contrast-enhanced T1-weighted magnetic resonance imaging (MRI) revealed an intramedullary lesion at T2-T3 with no contrast enhancement. The patient opted for conservative treatment. Eighteen months after the first consultation, the patient presented with slowly progressive numbness of the bilateral upper limbs, paraparesis, and dysuria, with rapid deterioration over the following 3 months. T1- and T2-weighted MRI revealed expansion of the intramedullary lesion, which extended from C7 to T5, and syringomyelia at C5-C6. Contrast-enhanced T1-weighted MRI revealed an enhancing intramedullary lesion at C7-T5. Open biopsy and C5-T5 laminectomy were performed for diagnosis and decompression. PA with anaplasia was diagnosed based on pathological and immunohistochemical findings. The patient received postoperative radiotherapy and chemotherapy. LESSONS: Rapidly progressive IMSC PA with a change in contrast enhancement is extremely rare in adults. PA may undergo a spontaneous malignant transformation during its natural clinical course. In this case, the change in contrast enhancement may have been associated with the malignant transformation of the PA.

True anaplastic oligoastrocytoma with dual genotype: illustrative case.

BACKGROUND: The revised fourth edition of the World Health Organization classification of central nervous system tumors was published in 2016. Based on this classification, one of the infiltrating glioma entities named "oligoastrocytoma/anaplastic oligoastrocytoma" is discouraged. It is proposed that these mixed gliomas should be classified as diffuse astrocytoma/anaplastic astrocytoma or oligodendroglioma/anaplastic oligodendroglioma when analyzing their genetic alteration. OBSERVATIONS: A 78-year-old female underwent brain computed tomography (CT) because of a traffic accident. Cranial CT revealed a brain tumor in the left temporoparietal lobe; therefore, she was hospitalized. She underwent awake craniotomy. After the operation, she was treated with only local radiotherapy; the authors could not prescribe temozolomide, because she had had levetiracetam-induced pancytopenia. The remaining tumor neuroradiologically disappeared, and she was alive 40 months after the operation without tumor recurrence. LESSONS: Histopathologically, this tumor was diagnosed as an anaplastic oligoastrocytoma with a distinct dual phenotype of astrocytoma and oligodendroglioma components. Genetically, these two components revealed astrocytoma and oligodendroglioma genotypes, respectively. Therefore, the authors considered the integrated diagnosis of the temporal tumor as a true anaplastic oligoastrocytoma with a dual genotype. Interestingly, this case also included an area composed of spindle to oval neoplastic cells that revealed intermediate genetic alterations between astrocytomas and oligodendrogliomas.

Role of proliferative marker index and KBTBD4 mutation in the pathological diagnosis of pineal parenchymal tumors.

Pineal parenchymal tumors (PPTs) are clinically rare and a biopsy is often required for a definitive diagnosis. To improve the accuracy of histological assessment of PPTs, we examined the proliferative capacity of PPT cells and investigated DICER1 expression and KBTBD4 mutations. This study included 19 cases of PPTs [3 pineocytomas (PCs), 10 PPTs of intermediate differentiation (PPTID), and 6 pineoblastomas (PBs)]. Immunohistochemistry for Ki-67, PHH3, and DICER1, as well as Sanger sequencing analysis for KBTBD4 mutations, was performed using formalin-fixed paraffin-embedded tissue specimens that were resected during surgery. Tumor cell proliferation was quantified using an image analysis software. For the PHH3 and MIB-1 indices, a significant difference was observed between the PPTIDs and PBs (P < 0.05). Loss of DICER1 was not specific for PB; 0/3 PCs (0.0%), 2/9 PPTIDs (22.2%), and 2/4 PBs (50.0%). KBTBD4 mutations were detected in 1/3 PCs (33.3%), 6/9 PPTIDs (66.7%), and 0/4 PBs (0.0%). Thus, combined application of the proliferative marker index and KBTBD4 mutation analysis may be useful for the differential diagnosis of PPTs. Furthermore, detection of KBTBD4 mutations using Sanger sequencing analysis may support the diagnosis of PPTID.

Cytopathological and histopathological features of cerebral granular cell astrocytoma: A case report.

This report describes the cytological features of granular cell astrocytoma (GCA), to aid in the diagnosis of intraoperative frozen samples of brain lesions, and discuss cytological similarities and differences between GCA, two significant non-neoplastic central nervous system lesions (brain infarction and demyelinating disorder), and three central nervous system tumours (gemistocytic astrocytoma, pleomorphic xanthoastrocytoma, and subependymal giant cell astrocytoma).

Droplet digital PCR assay for detecting TERT promoter mutations in patients with glioma.

Two hot spot mutations (C228T, C250T) in the telomerase reverse transcriptase (TERT) gene are frequently identified in glioblastoma and oligodendroglioma. TERT mutations predicts an aggressive clinical course in isocitrate dehydrogenase (IDH) wild-type astrocytic tumors. Therefore, it is important to accurately detect TERT promoter mutations in glioma. Sanger DNA sequencing is the currently standard method for analyzing TERT mutations. However, PCR amplification in the first step of the sequencing has proven technically difficult because of the high GC content around the TERT mutation. In this report, we described a novel droplet digital PCR (ddPCR) assay to evaluate TERT hot spot mutations in fresh frozen and formalin-fixed paraffin-embedded (FFPE) specimens of glioma and verified the difference in results from the Sanger DNA sequencing results. We obtained the mutant allele fraction for TERT mutations of in a single ddPCR run in all cases, including the micro-dissected FFPE sections. On the contrary, up to twice the DNA sequences were required from fresh frozen tissue to obtain the results, consistent with ddPCR assay. When FFPE specimens were used, more time was required to evaluate TERT mutations through DNA sequencing. DdPCR is an effective and sensitive assay compared to the conventional standard Sanger DNA sequencing.

Intracytoplasmic dot-like inclusions as cytopathologically useful findings of ependymoma: Case report of adolescent supratentorial anaplastic ependymoma with clear cell morphology.

Pediatric supratentorial ependymomas often have a clear cell morphology and reveal a RELA fusion. When a clear cell neoplasm is intraoperatively diagnosed, intracytoplasmic dot-like inclusions by cytology are a useful cytopathological feature of ependymoma.

Long-term survival of a patient with diffuse midline glioma in the pineal region: A case report and literature review.

BACKGROUND: Diffuse midline glioma (DMG) is an invasive astrocytic tumor arisen from midline structures, such as the pons and thalamus. Five cases of DMG in the pineal region have been reported, but the clinical course was poor; there was no case of survival for more than 2 years. CASE DESCRIPTION: We report the case of a 12-year-old boy with DMG in the pineal region who is living a normal daily life for more than 6 years following multimodal treatment. He complained of a headache accompanied by vomiting that had gradually worsened 1 month previously, and initial magnetic resonance imaging revealed a pineal tumor. Germinoma was initially suspected; however, a combination of chemotherapy using carboplatin and etoposide was ineffective. The first surgery was performed through the left occipital transtentorial approach (OTA); the diagnosis was DMG. After 60 Gy radiotherapy concomitant with temozolomide (TMZ), the tumor enlarged. Second surgery was performed through bilateral OTAs, and 90% of the tumor was removed. In addition, stereotactic radiotherapy (30 Gy, six fractions) was administered, and the local equivalent dose in 2 Gy/fraction reached 97.5 Gy. Maintenance chemotherapy using TMZ and bevacizumab was continued for 2 years. After finishing chemotherapy, the enhancing lesion enlarged again, and bevacizumab monotherapy was effective. Now, at 6 years after diagnosis, the patient leads an ordinary life as a student. CONCLUSION: Maximum resection and high-dose radiotherapy followed by bevacizumab may have been effective in the present case.

[Glioblastoma Mimicking Meningioma Recurrence: A Case Report].

Meningioma and glioma represent two common primary intracranial tumors. However, the coexistence of these two lesions in the same patient at the same location is rare. Here, we present a case of a fibroblastic meningioma with a secondary glioblastoma occurring at the same location. A 67-year-old woman underwent surgery for a left frontal parasagittal meningioma, and the tumor was subtotally removed. Two years and 11 months after the surgery, the patient had a tumor at the same location with invasion into the adjacent brain, suggesting recurrent meningioma with malignant transformation. The resected tumor was confirmed histopathologically as a glioblastoma. Genetic analysis revealed that the isocitrate dehydrogenase 1 and 2 genes were wild type, and the TERT promoter mutation was detected. The gene analysis suggests that the tumor was a de novo glioblastoma, not a secondary glioblastoma from a lower-grade glioma. (Received April 9, 2020; Accepted May 27, 2020; Published October 1, 2020).

An Epidermoid Cyst of the Thoracic Spine in an Elderly Patient.

BACKGROUND: Spinal epidermoid cysts are very rare tumors, especially in the thoracic spine; they represent 0.8% of all spinal epidermoids. In adult cases, they are often associated with surgical procedures such as lumbar puncture. We report a rare case of spinal epidermoid cyst in the thoracic spine of an elderly patient who had never undergone lumber puncture, thoracic spinal surgery, or trauma. CASE DESCRIPTION: A 78-year old woman presented with a 1-month history of rapidly progressive impairment of sensation in both the lower limbs, with gait disturbance. She had no history of spinal surgery, trauma, or lumbar puncture. Her past medical history was unremarkable. Magnetic resonance imaging of the whole spine revealed an intraspinalextramedullary tumor at the Th 1-2 level. Diffusion-weighted imaging revealed significant homogeneous high intensity. We performed complete resection without damaging the spinal cord or nerve roots. The final histological examination indicated epidermoid cyst without malignancy. Her gait disturbance was completely resolved at 4-month follow-up. CONCLUSIONS: Epidermoid cysts must be considered among spinal tumors in elderly patients. Early detection by diffusion-weighted imaging and complete resection may lead to good neurological outcome.

TERT promoter methylation is significantly associated with TERT upregulation and disease progression in pituitary adenomas.

PURPOSE: Alterations in the promoter of the telomerase reverse transcriptase (TERT) gene are a major mechanism of upregulating telomerase, which plays a crucial role in tumor development. Mutations in the TERT promoter have been observed in a subset of brain tumors, including adult gliomas and high-grade meningiomas. In pituitary adenomas (PAs), however, abnormalities in TERT are not fully understood. The present study aimed to investigate not only mutational but also methylation changes in the TERT promoter in PAs and to analyze their correlations with clinical variables. METHODS: We retrospectively studied 70 PAs consisting of 53 primary and 17 recurrent samples. Clinical data, including age at surgery, sex, largest tumor dimension, tumor subtype, resection rate, and progression-free survival (PFS), were obtained from medical records. We investigated TERT promoter hotspot mutations via Sanger sequencing and quantified the methylation status of the TERT promoter using methylation-sensitive high-resolution melting analysis (MS-HRM). Additionally, we investigated TERT mRNA expression using real-time quantitative PCR. RESULTS: TERT promoter hotspot mutations were not observed in any PA sample, while 16% of PAs exhibited TERT promoter methylation. PAs with methylated TERT promoters were significantly more likely to show disease progression, shorter PFS, and higher TERT expression levels compared to those with unmethylated promoters. CONCLUSIONS: This is the first study showing that TERT promoter methylation is associated with disease progression and shorter PFS as well as upregulated TERT expression in PAs. Our results suggest that TERT promoter methylation may be a potential biomarker for predicting tumor recurrence in PAs.

A Case of Suspicious Gangliocytoma with Heterogeneously Distributed Lesions in the Thalamus and Basal Ganglia.

We report a case of a 24-year-old woman who presented with an uncomfortable feeling in her right foot with a 6-month history of slight weakness in her right hand. Neuroimaging demonstrated irregular shaped lesions in the left thalamus and basal ganglia in addition to spotty lesions in the contralateral thalamus. The MRI showed high-intensity signals on T2-weighted, fluid-attenuated inversion recovery, and diffusion-weighted images. The lesions demonstrated low-intensity signaling on T1-weighted images and were slightly enhanced with gadolinium. Other examinations including positron emission tomography, MR spectroscopy, and laboratory tests did not reveal any specific information regarding the lesions. The biopsied specimens, from the left basal ganglia, revealed proliferation of dysplastic neuronal cells without any neoplastic glial elements; thus, gangliocytoma (WHO grade I) was the most likely diagnosis. The patient was further observed based on this diagnosis of suspicious gangliocytoma, and the follow-up MRI, performed a year after the biopsy, revealed that the disease was stable. To our knowledge, gangliocytoma in the thalamus and basal ganglia have not been reported. Additionally, the findings of the magnetic resonance imaging (MRI) in this case were unique and different from those previously reported in cases of gangliocytoma. The authors report this unique case and discuss the radiological, pathological, and genetic findings.

Novel, improved grading system(s) for IDH-mutant astrocytic gliomas.

According to the 2016 World Health Organization Classification of Tumors of the Central Nervous System (2016 CNS WHO), IDH-mutant astrocytic gliomas comprised WHO grade II diffuse astrocytoma, IDH-mutant (AIIIDHmut), WHO grade III anaplastic astrocytoma, IDH-mutant (AAIIIIDHmut), and WHO grade IV glioblastoma, IDH-mutant (GBMIDHmut). Notably, IDH gene status has been made the major criterion for classification while the manner of grading has remained unchanged: it is based on histological criteria that arose from studies which antedated knowledge of the importance of IDH status in diffuse astrocytic tumor prognostic assessment. Several studies have now demonstrated that the anticipated differences in survival between the newly defined AIIIDHmut and AAIIIIDHmut have lost their significance. In contrast, GBMIDHmut still exhibits a significantly worse outcome than its lower grade IDH-mutant counterparts. To address the problem of establishing prognostically significant grading for IDH-mutant astrocytic gliomas in the IDH era, we undertook a comprehensive study that included assessment of histological and genetic approaches to prognosis in these tumors. A discovery cohort of 211 IDH-mutant astrocytic gliomas with an extended observation was subjected to histological review, image analysis, and DNA methylation studies. Tumor group-specific methylation profiles and copy number variation (CNV) profiles were established for all gliomas. Algorithms for automated CNV analysis were developed. All tumors exhibiting 1p/19q codeletion were excluded from the series. We developed algorithms for grading, based on molecular, morphological and clinical data. Performance of these algorithms was compared with that of WHO grading. Three independent cohorts of 108, 154 and 224 IDH-mutant astrocytic gliomas were used to validate this approach. In the discovery cohort several molecular and clinical parameters were of prognostic relevance. Most relevant for overall survival (OS) was CDKN2A/B homozygous deletion. Other parameters with major influence were necrosis and the total number of CNV. Proliferation as assessed by mitotic count, which is a key parameter in 2016 CNS WHO grading, was of only minor influence. Employing the parameters most relevant for OS in our discovery set, we developed two models for grading these tumors. These models performed significantly better than WHO grading in both the discovery and the validation sets. Our novel algorithms for grading IDH-mutant astrocytic gliomas overcome the challenges caused by introduction of IDH status into the WHO classification of diffuse astrocytic tumors. We propose that these revised approaches be used for grading of these tumors and incorporated into future WHO criteria.

Craniospinal Germinomas in Patient with Down Syndrome Successfully Treated with Standard-Dose Chemotherapy and Craniospinal Irradiation: Case Report and Literature Review.

BACKGROUND: Patients with Down syndrome (DS) are more likely to develop chemotherapy-related complications. The standard treatment for these patients with cancer has not yet been established, and the risks of standard chemotherapy are unclear. In this paper, a rare case of multiple craniospinal germinomas in a patient with DS, which was successfully treated with standard-dose chemotherapy combined with craniospinal irradiation, is reported. CASE DESCRIPTION: The authors report a case of multiple craniospinal germinomas in a DS patient who presented with bilateral oculomotor and facial nerve palsy and hearing loss. The patient underwent 3 courses of combination chemotherapy using a standard dose of carboplatin and etoposide and 23.4 Gy of concurrent craniospinal irradiation. Posttreatment magnetic resonance imaging showed reduction of the tumors. Both fluorodeoxyglucose- and methionine-positron emission tomography demonstrated no uptake in the residual tumors. Follow-up magnetic resonance imaging and positron emission tomography did not reveal tumor recurrence for 18 months. CONCLUSIONS: As far as we know, this is the first case of multiple craniospinal germinomas in a patient with DS who achieved a successful treatment result without fatal adverse events. The literature review indicated that disseminated germinomas may need intensive treatment to reduce recurrence risk. However, intensive chemotherapy using a combination of 3 or more anticancer drugs can increase the rate of treatment-related death during the early stage. Our case indicated that multiple craniospinal germinoma of DS patients could be treated with a standard dose of carboplatin and etoposide regimen with concurrent craniospinal irradiation along with appropriate supportive therapy and careful observation.