[A Case of Bone Marrow Metastasis of Oligodendroglioma with IDH Mutation and 1p/19q Codeletion].

A 71-year-old woman was transferred to our hospital, complaining of a seizure for the first time. A tumor was detected in the right frontal lobe, and a craniotomy was performed with a partial tumor resection. The pathological diagnosis was oligodendroglioma with IDH mutation and 1p/19q codeletion, and irradiation therapy was performed. Six months later, the patient's lactate dehydrogenase(LDH)level elevated remarkably, and the fluoro-deoxyglucose-positron emission tomography/computed tomography showed abnormal uptake in multiple bone marrow locations. Bone marrow aspiration was performed, and the pathological diagnosis was oligodendroglioma metastasis. The patient was given two cycles of chemotherapy with temozolomide(TMZ), and her LDH level reduced to normal. After a few months, the LDH level elevated again, so we gave her two more cycles of TMZ;however, her LDH level did not change. Thereafter, the patient was hospitalized because of paraplegia, which started a few days prior, and right lower jaw swelling. Her CT and magnetic resonance imaging showed metastasis to the thoracic vertebrae and right mandibular bone. Irradiation therapy was performed to these locations, and the patient was given chemotherapy using nimustine(ACNU), procarbazine, and vincristine(PAV). Her LDH levels reduced temporarily, but elevated again. The patient deteriorated slowly and died 20 months after she presented with a seizure. Oligodendroglioma with extracranial metastasis is extremely rare, and this case report is the 68th report. The chemotherapy approach with TMZ or PAV/PCV may be effective against oligodendroglioma metastasis to the bone marrow.

Extracranial metastatic oligodendroglioma with molecular progression, case presentation.

BACKGROUND: Extraneural metastasis of central nervous system tumors is generally rare and most often reported in glioblastomas and medulloblastomas, whereas oligodendrogliomas seem to have the lowest risk of extracranial metastasis. Given its infrequent occurrence, both the diagnosis and therapy of metastatic oligodendroglioma is often challenging. CASE PRESENTATION: This case study presents an oligodendroglioma, the isocitrate dehydrogenase 1 (IDH1) mutant, 1p/19q-codeleted tumor with bone marrow metastasis. The significance of this case lies in the comprehensive molecular analysis conducted for both the primary tumor and the metastasis. Chromosome 7 trisomy and chromosome 10 monosomy (+ 7/-10) were detected in the metastasis indicating molecular progression, which, to the best of our knowledge, has not been previously documented in metastatic oligodendroglioma. CONCLUSIONS: This case study serves additional information for better understanding of the metastatic capabilities of CNS tumors.

Oligodendroglioma metastasizing to cervical lymph node: Rare entity diagnosed on fine-needle aspiration cytology.

Extra neural metastasis of central nervous system oligodendroglioma is very rare. Oligodendroglioma is the seventh most frequently occurring neoplasm of central nervous system (CNS) with metastasis outside the CNS. According to literature, presence of metastasis in CNS was most frequently detected in patients of glioblastoma (41.4%), medulloblastoma (26.7%), ependymomas (16.4%), astrocytoma (10.3%) and oligodendroglioma (5.27%). A 38-year-old male patient presented with loss of vision and swelling on left side of neck since last 1 week measuring 3 x 2 cm. He was operated for brain tumor 7 years back, which was diagnosed as oligodendroglioma. Ultrasound sonography revealed multiple hypoechoic lymph nodes in bilateral cervical region largest measuring 4.5 x 1.9 cm in left submandibular region. FNA of left submandibular lymph node was done, which revealed deposits of poorly differentiated malignancy. Cell block was prepared for carrying out ancillary studies which showed positivity for glial fibrillary acidic protein (GFAP), S-100 and negativity for cytokeratin (CK), epithelial membrane antigen (EMA), LCA and progesterone receptor (PR). Based on previous history of oligodendroglioma, cytological and immunohistochemistry (IHC) findings a diagnosis of metastatic oligodendroglioma was made. Metastasis of oligodendroglioma to cervical lymph node should also be considered as one of the differential diagnoses. Diagnosing metastatic CNS tumor is extremely challenging for pathologists. It is essential to have the clinical information of a previous CNS tumor, including the histologic type and immunophenotype. Besides common malignancies of cervical lymph node, we should also think of CNS metastasis so that patient management will be early and proper.

Fine-needle aspiration cytology of metastatic oligodendroglioma: case report and literature review.

BACKGROUND: Systemic metastasis of a glial tumor is a rare event. However, metastatic cases are anticipated to increase due to prolongation of survival as a result of the development of new treatment modalities. The possibility of metastasis should be considered in patients with a history of a glial tumor rather than a second primary tumor. Fine-needle aspiration cytology is one of the diagnostic procedures primarily applied for confirmation of metastasis in cases with a known primary focus. Therefore, comprehensive knowledge of diagnostic cytomorphologic findings is required in these cases. CASE REPORT: We report a young woman with oligodendroglioma metastasizing to the cervical lymphatic chain 5 years after initial diagnosis. Fine-needle aspiration cytology revealed a highly cellular smear with dispersed single cells and loosely cohesive cell clusters showing rosette-like features on a clean background. The relatively monotonous tumor cells were small sized and had round nuclei with moderate anisonucleosis and scant cytoplasm without extensions. Diagnostic confirmation was made by excisional biopsy and demonstration of 1p19q codeletion on tissue section by fluorescence in situ hybridization. CONCLUSION: A brief review of the literature with an emphasis on the cytologic features of metastatic oligodendroglioma and differential diagnosis with respect to other metastatic small round cell tumors is provided.

Paraplegia due to drop metastases from anaplastic oligodendroglioma.

In this article, we report on a rare case of spinal seeding from a cerebral anaplastic oligodendroglioma presenting with signs of medullar compression. We discuss the prevalence, mechanisms and imaging findings of spinal seeding in various gliomas. A suitable clinical treatment and follow up for these patients is suggested.

Symptomatic Spinal Seeding Metastasis of a Low-grade Oligodendroglioma.

Extracranial metastases from primary brain tumours are mostly caused by high-grade tumours. Metastases from low-grade intracranial tumours are much rare and usually asymptomatic. We present a case of a symptomatic spinal cord compression with intradural extramedullary and diffuse leptomeningeal infiltration observed approximately 51 months after the first diagnosis of a 52-year male patient with WHO Grade 2 oligodendroglioma with temporoparietal localisation. This patient, who had the complaint of weakness in the lower extremity, was operated on due to a thoracic intradural extramedullary mass. The result of the pathological examination came out as WHO Grade 2 oligodendroglioma, and radiotherapy was planned for this seeding metastasis. The patient who experienced refractory seizures died before his radiotherapy treatment was completed. It should be kept in mind that spinal metastases may also be seen in low-grade intracranial tumours without malignant transformation as in the present case. Key Words: Spinal seeding, Spinal metastases, Low-grade oligodendroglioma.

Detection of IDH1 mutations in gliomatosis cerebri, but only in tumors with additional solid component: evidence for molecular subtypes.

The current WHO classification of brain tumors defines gliomatosis cerebri (GC) as an extensively infiltrating astrocytic glioma involving at least three cerebral lobes. The relation of GC to diffuse astrocytomas and glioblastoma is uncertain. Due to malignant biological behavior, GC is allotted to WHO grade III. Recent reports showed IDH1 mutations in astrocytic and oligodendroglial tumors WHO grades II and III and in secondary glioblastomas with a frequency of up to 90%, whereas IDH1 mutations occurred in only 5% of primary glioblastomas. Here, we examined the frequency of IDH1 mutations in 35 GC samples by direct sequencing, derived cleaved amplified polymorphic sequence analysis and immunohistochemistry. We identified IDH1 mutations in 10/24 (42%) cases, which also included a solid tumor portion (type 2 GC), but not in 11 "classical" cases without solid tumor mass (type 1 GC). TP53 mutations were revealed in two type 2 GC, but not in any type 1 GC, while combined chromosomal losses of 1p and 19q were not found at all. Our data suggest that GC consists of two histological/molecular subtypes, type 1 being clearly distinct from diffuse astrocytoma, and type 2 sharing features with diffuse astrocytoma.

Metastatic oligodendroglioma: a case report and incidence in The Netherlands.

Oligodendroglioma is a tumor of the central nervous system which rarely metastasizes. The diagnosis of oligodendroglioma is based on histomorphology with limited use of immunohistochemistry. However, recently a specific 1p/19q codeletion has been found which can be demonstrated by in situ hybridization. We report a case of a 58-years-old man with a 31-months history of oligodendroglioma presenting with fatigue and anemia. A bone marrow biopsy demonstrated massive localization of oligodendroglioma which was confirmed by in situ hybridization for the 1p/19q deletion. In addition we studied data from PALGA, the nationwide network and registry of histo- and cytopathology in the Netherlands and found an incidence of approximately 2 in 1,000 for metastasis of oligodendroglioma outside the central nervous system.

Successful treatment of a BRAF V600E-mutant extracranial metastatic anaplastic oligoastrocytoma with vemurafenib and everolimus.

BACKGROUND: Extracranial metastasis is a rare phenomenon of anaplastic oligoastrocytoma. When patients progress after comprehensive treatment, there is often no effective treatment. Rapid development of gene detection technology makes precision treatment of glioma possible. PATIENT AND METHODS: A 22-year-old girl was firstly diagnosed with anaplastic oligoastrocytoma WHO grade III-IV in 2014, and progressed rapidly after chemoradiotherapy in multiple extraneural lesions in 2016. She was expected to have a short life and Next-Generation Sequencing (NGS) was applied. RESULTS: Mutation of BRAF (V600E) was reported by 1st NGS and oral vemurafenib stabilized her disease for 6 months. PIK3CA was reported by 2nd NGS after her progression of vemurafenib. The oral administration of everolimus together with vemurafenib stabilized her disease for another 6 months. However, the patient died due to the rapid progression of the disease on 24 February 2018. CONCLUSION: We successfully treated a BRAF V600E-mutated anaplastic oligoastrocytoma with multiple extraneural metastases with vemurafenib and everolimus. For late-staged patients who have no clear and effective treatment plan, NGS may serve as an effective option.

Bone metastases from a 1p/19q codeleted and IDH1-mutant anaplastic oligodendroglioma: a case report.

BACKGROUND: Oligodendroglioma is a rare type of primary brain tumor which, like other malignant gliomas, metastasizes very rarely even when in high-grade form. CASE REPORT: A 36-year-old white man diagnosed 29 months previously as having 1p/19q codeleted anaplastic oligodendroglioma presented bilateral cruralgia and lower limb motor deficits. A computed tomography scan showed multiple osteoblastic bone lesions. The presence of oligodendroglial cells was revealed by bone marrow biopsy and confirmed by immunohistochemical analyses. A positon emission tomography-computed tomography scan confirmed the exclusive involvement of bones. CONCLUSION: This case joins less than 20 other reported cases of oligodendroglioma bone marrow metastasis, and is one of only a handful of cases of diffuse bone metastases beyond the axial skeleton. To the best of our knowledge, the early relapse of 1p/19q codeleted anaplastic oligodendroglioma with this distribution of metastases has never been described in the literature.

Leptomeningeal metastases in glioma: The Memorial Sloan Kettering Cancer Center experience.

OBJECTIVE: To perform a retrospective analysis examining the incidence and prognosis of glioma patients with leptomeningeal disease (LMD) at Memorial Sloan Kettering Cancer Center over a 15-year period and correlate these findings with clinicopathologic characteristics. METHODS: We conducted a retrospective review of glioma patients with LMD at Memorial Sloan Kettering Cancer Center diagnosed from 2001 to 2016. Patients were identified through a keyword search of their electronic medical record and by ICD-9 codes. RESULTS: One hundred three patients were identified with disseminated LMD and 85 patients with subependymal spread of disease, 4.7% of all patients with glioma. These cohorts were analyzed separately for time to development of disseminated LMD/subependymal LMD, median overall survival, and survival from LMD diagnosis. Patients were pooled for subsequent analyses (n = 188) because of comparable clinical behavior. LMD was present at glioma diagnosis in 10% of patients. In the remaining 90% of patients diagnosed at recurrence, time to LMD diagnosis, survival after LMD diagnosis, and overall survival varied by original histology. Patients with oligodendroglioma had a median survival of 10.8 (range 1.8-67.7) months, astrocytoma 6.5 (0.1-28.5) months, and glioblastoma 3.8 (0.1-32.6) months after LMD diagnosis. In addition, we found that treatment of LMD was associated with superior performance status and increased survival. CONCLUSION: Patients with LMD diagnosed at relapse may not have decreased overall survival as compared to historical controls with parenchymal relapse and may benefit from treatment.

Scalp Metastasis of Anaplastic Oligodendroglioma.

BACKGROUND: Scalp metastases from anaplastic oligodendroglioma (AO) are extremely rare and mostly involve intracranial recurrence or widely metastatic disease. Here we describe an exceptional case of histopathologically proven scalp metastasis of AO 6 years after surgical resection and postoperative adjuvant radiation. CASE DESCRIPTION: A 42-year-old woman presented with several months of progressive headache and dizziness. Preoperative magnetic resonance imaging (MRI) showed an irregular enhancing lesion in the left frontal lobe extending to the ependymal surface. Left frontal craniotomy was performed through a coronal approach, and gross total resection was achieved. Pathologic examination confirmed a World Health Organization grade III AO. The patient subsequently received 60 Gy of external beam radiotherapy in 30 fractions over 6 weeks. During 8 years of follow-up, the patient remained symptom free, and no evidence of intracranial recurrence was found. However, 6 years after intracranial tumor resection, the patient noticed a subcutaneous mass in her right frontal scalp, which was the site contralateral to her craniotomy. MRI revealed a homogeneously marked enhancing nodular lesion in the subcutaneous tissue of the right frontal scalp without intracranial recurrence. Gross total resection was performed, and the pathologic findings, which identified the mass as an AO, were consistent with those of the primary left frontal tumor. CONCLUSIONS: This study presents a rare case of long-term AO scalp metastasis without intracranial recurrence. Intraoperative seeding and longer survival for oligodendroglial tumors may cause this rare entity. Optimal surgical strategies and standard operative procedures can promote the prevention of iatrogenic seeding.

Metastatic oligodendrogliomas: a review of the literature and case report.

Oligodendroglioma cells are detectable in the cerebro-spinal fluid in up to 14% of patients [10] and cerebellar and/or spinal cord involvement is a well known phenomenon [3]. Distant spread of oligodendroglioma is exceptional, probably due to the presence of the blood-brain barrier, the absence of lymphatic vessels and the short survival of patients. A review of the worldwide literature yielded 32 previously reported examples since 1951 to the present (Tab1e 1). This review was performed using NCBI-PubMed and "oligodendroglioma, oligodendrogliomas, metastatic, metastasis, metastases, extraneural", in different combinations, as key words and reviewing the bibliography of the consequent selected articles. New therapeutic approaches are prolonging the overall survival of patients with primitive brain tumours and in particular of those with high grade oligodendroglioma which is a chemo-sensitive disease. A longer overall survival could increase the risk of extracranial dissemination of gliomas that in the future might become a less rare clinical complication.

Anaplastic oligodendroglioma with meningeal infiltration in a free-ranging red deer (Cervus elaphus).

This report describes an anaplastic oligodendroglioma in a red deer, extending from the cerebellum and anterior medulla along the dorsal part of the brain stem to the posterior cerebral hemispheres and infiltrating the meninges. Immunohistologically, the tumour cells were labelled for S-100 but were negative for glial fibrillary acidic protein, vimentin and synaptophysin. This would appear to be the first report of an oligodendroglioma in a deer.

Unusual massive spinal metastasis of an intracranial oligodendroglioma.

Herein, we present a case of anaplastic oligodendroglioma with massive spinal metastasis in the first post-operative year without any residual tumor or recurrence in the primary tumor site. Along with the reported literature, our case highlights the importance of periodic radiological evaluation of the spinal canal including the pre- and post-treatment period, in patients with intracerebral oligodendroglioma.

Predominant expression of OLIG2 over ID2 in oligodendroglial tumors.

OLIG2 is a basic helix-loop-helix transcription factor regulating the generation of oligodendrocytes from neural progenitor cells, and the function of OLIG2 is inhibited posttranslationally through the interaction with ID2. This study aims to examine if the analysis of OLIG2 and ID2 expression in glioma tissues helps the differential diagnosis of chemosensitive oligodendroglial tumors from astrocytic tumors. Expression levels of OLIG2 and ID2 in 11 oligodendroglial and 27 astrocytic tumors were analyzed by reverse transcription-polymerase chain reaction (RT-PCR), real-time quantitative PCR, and immunohistochemistry. The mean expression level of OLIG2 was higher in oligodendroglial tumors than astrocytic tumors, but some astrocytic tumors showed high OLIG2 expression, indicating that OLIG2 cannot be an independent marker of oligodendroglial tumors. No significant difference was observed between ID2 expression in oligodendroglial tumors and astrocytic tumors. It was notable that OLIG2 expression was predominant over ID2 expression in oligodendroglial tumors, while ID2 expression was predominant over OLIG2 expression in astrocytic tumors. Comparative genomic hybridization revealed that gliomas with loss on chromosome 1p, which is closely associated with chemosensitivity, also showed the predominant expression of OLIG2 over ID2. These results indicate that the immunohistochemical study on the relative expression level of OLIG2 to ID2 can be a useful screening for oligodendroglial tumors.

Intracranial dissemination of primary spinal cord anaplastic oligodendroglioma.

We report the first case of a 22-year-old man, with a previously neurosurgically treated intramedullary anaplastic oligodendroglioma (World Health Organization grade III), who developed 19 months later two histologically proven intracranial metastases. We support a hypothesis whereby the anaplastic parts of tumors have spread along the spinal cord and brainstem via the cerebrospinal fluid pathways, a process that could be promoted by surgical manipulation, although the relative contribution of the two factors remains speculative.

A methionine-free diet associated with nitrosourea treatment down-regulates methylguanine-DNA methyl transferase activity in patients with metastatic cancer.

BACKGROUND: Methionine (MET) depletion used in association with chemotherapy improves the therapeutic index in animal models. This potentiating effect may be due to tumor cell sensitization to chloroethylnitrosoureas through their MET dependency and the down-regulation of O6- methylguanine-DNA methyltransferase (MGMT). Our purpose was to evaluate the impact of the association of a dietary MET restriction with nitrosourea treatment on MGMT activity in peripheral blood mononuclear cells (PBMCs). PATIENTS AND METHODS: Six patients with metastatic cancer (melanoma and glioma) received 4 cycles of a MET-free diet with cystemustine (60 mg/m2). RESULTS: MGMT activity in PBMCs decreased by an average of 13% from 553+/-90 fnol/mg before the diet to 413+/-59 fmol/mg after the diet + chemotherapy period (p=0.029). The decrease of MGMT activity was not affected by the duration of the MET-free diet period but seems to be correlated to the plasma MET depletion induced by the MET-free diet.

Frontal anaplastic oligodendroglioma showing multi-organ metastases after a long clinical course. Case report.

A 17-year-old woman presented with an anaplastic oligodendroglioma manifesting as generalized seizure. Neuroimaging studies revealed a right frontal tumor. Histological examinations of biopsy specimens revealed that the tumor was oligodendroglial in nature. Total resection was repeated four times, and malignant change was evident within the tissues. The final diagnosis was anaplastic oligodendroglioma. Despite irradiation, combination chemotherapy, and interstitial hyperthermia, the tumor grew rapidly but was confined to the cavity created by previous removal operations. She suffered bone pain in the last 3 months of her life, when neuroimaging examinations disclosed multiple bone lesions. She died at the age of 29 years. At autopsy, generalized metastases from the tumor were identified at various sites, including the dura mater covering the frontal lobes and thoracic cord, cavernous sinus, tuberculum sellae, spleen, liver, pancreas, lungs, paratracheal lymph nodes, vertebral bodies, ribs, sternum, pelvis, dorsal root ganglia, and iliopsoas muscle. This rare case of cerebral anaplastic oligodendroglioma developed in adolescence, and rapid hematogenous spread of the glioma cells into the systemic organs occurred after a relatively long clinical course.