Temporal Glioblastoma Multiforme Research Articles

Glioblastoma multiforme with metastasis to lung, bone, and chest wall: a case report

Abstract Glioblastoma multiforme (GBM) is a common brain tumor that rarely metastasizes extra-cranially. We present the case of a 40-year-old male with left temporal GBM who underwent craniotomy followed by radiotherapy and chemotherapy. Postoperative MRI scans at different time intervals demonstrated a good response. Eleven months after the initial diagnosis, there were no clinical or radiological signs suggesting recurrence. However, the tumor showed metastasis simultaneously to the chest wall, lungs, and bone, despite 2 cycles of chemotherapy. The patient developed paraplegia 14 months after the initial diagnosis and died due to systemic failure 19 months after diagnosis. Extracranial metastasis of GBM is extremely rare. We present the unusual case of a patient with GBM who showed simultaneous metastasis to the lungs, bone, and chest wall. The prognosis of patients with extracranial metastasis of glioblastomas is very poor, regardless of chemoradiotherapy. Newer approaches, such as immunotherapy and anti-angiogenic therapy, need to be further studied.

1643 Colonic Malakoplakia: An Exquisitely Rare Cause of Lower GI Bleeding

INTRODUCTION: Malakoplakia is a rare chronic granulomatous disease that may affect many organs. The gastrointestinal tract is the second most common site of involvement (after the urinary tract). The most common sites of colonic involvement are the rectum, sigmoid, and right colon, in descending order of frequency. The pathogenesis of malakoplakia is unknown. The treatment of malakoplakia ranges from antibiotic therapy to surgical resection. Here we describe a case of a 33-year-old man who presented with hematochezia and was noted to have malakoplakia on rectal mass biopsy during colonoscopy. CASE DESCRIPTION/METHODS: A 33-year-old man presented to our clinic due recurrent episodes of painless hematochezia in the setting of warfarin for recent lower extremity deep venous thrombosis. He is a resident of a nursing home due to a complex neurosurgical history which includes resection of a right temporal glioblastoma multiforme tumor followed by chemo and radiation therapy. He also had subsequent craniotomy and ventriculo-peritoneal shunt placement and used oral dexamethasone for recurrent episodes of cerebral edema related to residual brain tumor. Despite stopping warfarin he continued to have rectal bleeding. Colonoscopy showed a frond-like/villous, fungating and polypoid non-obstructing circumferential mass in the rectum. Biopsies showed malakoplakia. After multidisciplinary discussions, a decision was made to continue dexamethasone to minimize cerebral edema and bowel resection was declined by patient’s parents. We opted to use a prolonged course of Ciprofloxacin, however, the patient developed severe urosepsis and unfortunately died. DISCUSSION: First reported by Michaelis and Gutmann in 1902, malakoplakia is derived from the Greek “malakos” (soft) and “plakos” (plaque) and reflects its usual endoscopic appearance as a friable, yellow mucosal lesion. Coliform bacteria in macrophage cytoplasm (von Hansemann histiocytes), and laminated intracytoplasmic inclusion bodies (Michaelis-Gutmann bodies) are characteristic. A decrease in macrophage cyclic GMP activity with resultant impaired bactericidal activity is hypothesized to be the cause of malakoplakia. Macrophage abnormalities and clinical symptoms resolve after discontinuation of glucocorticoids. Antibiotics such as ciprofloxacin have been successful treatments in few case reports. Unfortunately our patient did not have the opportunity to utilize any of these antibiotics prior to his passing.

Histologic findings associated with laser interstitial thermotherapy for glioblastoma multiforme

BackgroundLaser-interstitial thermal therapy (LITT) has been supported by some authors as an ablative treatment of glioblastoma multiforme (GBM). Although the effects of LITT have been modeled in vivo, the histologic effects in a clinical circumstance have not been described. We analyzed tissue from a patient who underwent LITT as primary treatment for GBM.Case presentationA 62-year-old male was diagnosed with a left temporal GBM and underwent LITT at an outside institution. Despite corticosteroid therapy, the patient was referred with increasing headache and acalculia associated with progressive peritumoral edema two weeks after LITT procedure. En bloc resection of the enhancing lesion and adjacent temporal lobe was performed with steroid-independent symptom resolution (follow-up, > 2 years). Histologic analysis revealed three distinct histologic zones concentrically radiating from the center of the treatment site. An acellular central region of necrosis (Zone 1) was surrounded by a rim of granulation tissue with macrophages (CD68) (Zone 2; mean thickness, 1.3 ± 0.3 mm [±S.D.]). Viable tumor cells (identified by Ki-67, p53 and Olig2 immunohistochemistry) were found (Zone 3) immediately adjacent to granulation tissue. The histologic volume of thermal tissue ablation/granulation was consistent with preoperative (pre-resection) magnetic resonance (MR)-imaging.ConclusionThese findings are the first in vivo in humans to reveal that LITT causes a defined pattern of tissue necrosis, concentric destruction of tumor and tissue with viable tumor cells just beyond the zones of central necrosis and granulation. Furthermore, MR-imaging appears to be an accurate surrogate of tissue/tumor ablation in the early period (2 weeks) post-LITT treatment. Surgery is an effective strategy for patients with post-LITT swelling which does not respond to steroids.

A case of recurrent gliosarcoma mimicking subdural hematoma

Abstract The authors present the case of a patient who after undergoing craniotomy for glioblastoma resection was found to have gliosarcoma recurrence in the subdural space without intraparenchymal recurrence. A 74-year old man originally presented with the first seizure of his life and was found to have a right temporal glioblastoma multiforme. He underwent craniotomy and adjuvant chemotherapy and radiation therapy. Five months later, he presented with what was to be presumed to be a right subdural hematoma found on surveillance imaging. After expanding on repeat imaging, the patient was electively taken for burr hole evacuation, however intraoperatively thickened membranes were encountered leading to craniotomy and resection of lesion with pathology consistent with gliosarcoma. What we describe is novel because not only was there rare subdural spread of previously resected glioblastoma observed, but also transformation to the more aggressive tumor of gliosarcoma. Thus, we add to the body of literature and evidence to the clinical consideration of glioma as a rare cause of non-traumatic subdural collection. Specifically in a population of patients who have already undergone glioma resections, work up of subdural collections should include contrasted MRI beyond CT. The treatment paradigm does not change in this presentation of glioma recurrence. Surgical decompression and resection to alleviate brain compression, followed by adjuvant chemotherapy and radiation.

Abstract 1318: Mapping tumoral and immune heterogeneity in PD-1 responsive glioblastoma multiforme

Abstract Background and aims: Clonal evolution and the immune microenvironment in glioblastoma multiforme (GBM) harbor critical clues to its well-known but poorly understood treatment resistance, and to assessing the potential benefit of checkpoint inhibition. We created a tumor-immune interaction map by computing the mutational and neo-epitope tumoral burden, along with the magnitude and clonality of infiltrating lymphocytes, from initial and recurrent tumor of a single patient who benefited from PD-1 blockade. The question of how this particular GBM evolution trajectory compares to a typical GBM is addressed by projection of mutational and other signatures onto a causal gene-gene interaction network we derived from the TCGA GBM cohort. Methods: We compiled samples from a 57- year-old patient who presented with a seizure and had a resection of a large temporal GBM followed by radiotherapy with concurrent temozolomide, with subsequent re-resection for recurrent disease. Starting two weeks after the final resection the patient received 26 cycles of a PD-1 checkpoint inhibitor simultaneous with 20 cycles of bevacizumab, a VEGF-A inhibitor, for a total survival of 25 months after diagnosis. Samples from the primary and three spatial sectors of the recurrence were submitted for RNA sequencing. Data analyses included intra-tumoral gene expression including MHC-I and MHC-II allele-specific expression, expressed relative mutation and (class I and class II) neo-epitope prediction, T and B cell receptor sequencing, and survival and molecular analysis on the GBM TCGA dataset. Results and Conclusions: We quantified the evolving relative mutational and neo-epitope burden of a GBM, emphasizing the differences between class I and class II neo-epitope spectra and resulting adaptive immune recruitment between the original and recurrent tumor regions. We find no evidence of hypermutation in the recurrence, a relative absence of immune infiltration in all recurrences despite the expression of a number of neo-epitope generating mutations (including a novel clonal mutation of EGFR), and compelling evidence of epigenetically driven aberrations in one recurrence sector. Hypothesizing significant molecular heterogeneity as a result of immune editing and treatment, we derived a tumor-recurrence molecular evolution trajectory and projected it onto a Bayesian inference network we derived from the TCGA GBM cohort. We quantified intra-tumoral heterogeneity, derived a patient survival signature, and also identified immunogenic mutated gene regulatory subnetworks that could be potentially targeted by any induced robust immune response. Citation Format: Bojan Losic, Raymund Yong, Nicholas Akers, Ilaria Laface, Nadejda Tsankova, Robert Sebra, Sacha Gnjatic, Adilia Hormigo. Mapping tumoral and immune heterogeneity in PD-1 responsive glioblastoma multiforme [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1318.

Hypertensive-Nimodipine Therapy for Middle Cerebral Artery Vasospasm after Resection of Glioblastoma Multiforme: A Case Report and Literature Review

Delayed cerebral ischemia (DCI) due to post-brain tumor resection vasospasm is an often unrecognized yet debilitating complication. We present a patient with DCI after the resection of glioblastoma multiforme (GBM). To our knowledge, this is the first report on DCI after GBM resection. A 52-year-old female patient with headache for one month underwent subtotal resection of a left temporal GBM encasing the proximal middle cerebral artery (MCA). She was well during the immediate postoperative period but developed right upper limb dense monoparesis on postoperative day four with computed tomographic angiography confirming left MCA vasospasm. Symptoms were significantly alleviated with weeklong hypertensive therapy and nimodipine administration; however they recurred soon after cessation of treatment. A high index of clinical suspicion is needed for the diagnosis of post-tumor resection DCI. Any new postoperative neurological deficit that cannot be explained by hemorrhage, seizures or infection should be expeditiously investigated by angiography or transcranial Doppler sonography. Prompt initiation of hypertensive and nimodipine therapy can possibly reverse neurological deficit. Treatment should be guided by Doppler, angiographic or perfusion imaging studies and not by clinical improvement alone.

Cervical intramedullary metastasis from cerebral glioblastoma multiforme: Case report

Glioblastoma multiforme (GBM) is usually characterized by diffuse, infiltrative growth and local tumor progression. Extensive leptomeningeal metastases are rarely observed. It is unclear which GBMs are prone to this specific growth pattern and progression, and standardized salvage treatment protocols are unavailable.In a 45-year-old man without focal neurologic deficit, a right temporal GBM, IDH-wildtype (biomarkers MGMT promoter methylation negative, Ki-67 proliferation rate 70%) was diagnosed. Gross tumor resection followed by concomitant and adjuvant radiotherapy and chemotherapy with temozolomide was performed. Routine follow-up imaging 8 months later showed a right parietal meningeal tumor. Resection confirmed a distant GBM, and next-generation sequencing revealed high tumor mutational burden, high-frequency microsatellite instability, and a pharmacologically targetable KIT mutation. Complete neuraxis imaging revealed multiple contrast-enhancing tumors in the craniocervical junction and levels C7, Th8-Th11, and S1. The craniocervical tumors and the cervical spine from C1-C2 were irradiated as palliative care, and second-line combined chemotherapy and antiangiogenic therapy with irinotecan and bevacizumab was initiated, which was later changed to an immune-checkpoint blockade with pembrolizumab in combination with bevacizumab owing to tumor progression. Tumor growth was slowed, but the patient eventually developed a progressive paraparesis. Subsequent KIT-targeting tyrosine kinase inhibitor therapy with imatinib was administered for a short time. The patient died 13.8 months after initial diagnosis.High-risk genetic profiles for GBMs prone to develop extensive leptomeningeal metastases need to be identified. Guidelines on preemptive, complete neuraxis imaging in certain patients with GBM as well as treatment guidelines need to be developed.

Recurrent glioblastoma multiforme presents as a mirror image in the contralateral temporal lobe

A 44-year-old woman with history of left temporal glioblastoma multiforme (GBM) presented with a generalized seizure and altered mental status. She had undergone surgical resection for the left tem...

Pearls & Oy-sters: Large vessel ischemic stroke secondary to glioblastoma multiforme

A 41-year-old right-handed nonsmoker with glioblastoma multiforme and no known vascular risk factors developed sudden onset right upper extremity weakness 7 months after he was diagnosed with left temporal glioblastoma multiforme by stereotactic biopsy, 5 months after treatment with radiation therapy and temozolomide, and 4 months after gross total resection with placement of Gliadel™ wafers. His past medical history was negative for hypertension, hyperlipidemia, diabetes, or coronary artery disease. On examination, he was unable to lift his right arm against gravity. MRI revealed a left corona radiata infarct. Gadolinium-enhanced T1 images revealed complete occlusion of the left middle cerebral artery (MCA) at M1 (figure, A). No secondary stroke prevention therapy was initiated. Two months …

De novo cerebellar medulloblastoma in a 26-year recurrence-free case of temporal glioblastoma multiforme

The authors describe a patient who survived 26 years after resection of a right temporal glioblastoma multiforme (GBM) without signs of tumor recurrence. Preoperative emergency angiography demonstrated a hypovascular mass localized in the right temporal lobe with right-to-left shift of the vascular structures. At surgery, the tumor had cystic and solid components localized in the lateral occipitotemporal gyrus, reaching the posterolateral wall of the inferior horn of the right lateral ventricle and extending to the trigone and posterior horn. The initial pathological diagnosis of a GBM was reviewed and confirmed throughout the follow-up period. Twenty-six years after surgery and subsequent radiosurgery, the patient underwent resection of a medulloblastoma localized in the right cerebellum as well as stereotactic biopsy sampling of tissue at the original GBM site. Neither radiological nor histological evidence of recurrence of the GBM could be documented. The intraoperative, histological, and radiological findings are described.

Diffuse vertebral body metastasis from a glioblastoma multiforme: a technetium-99m Sestamibi single-photon emission computerized tomography study

The authors report on a case of right temporal glioblastoma multiforme (GBM) that metastasized to multiple bone regions (dorsolumbar vertebrae and iliac bone) 8 months after initial diagnosis, despite combined radio- and chemotherapy. Results of a whole-bone single-photon emission computerized tomography (SPECT) study using the imaging agent Sestamibi (MIBI) revealed extracranial metastases from the GBM. A magnetic resonance imaging study of the dorsolumbar spinal region completed the radiological investigation. Cells immunoreactive to glial fibrillary acidic protein were observed in a specimen obtained from the right iliac bone. Postmortem examination confirmed metastasis to extracranial bone and revealed two other metastatic localizations in the lung and heart. This is the first reported case of extracranial bone metastasis from a GBM demonstrated on a whole-bone MIBI SPECT scan. In patients with malignant glioma and lower-back pain (especially prolonged pain), bone metastasis, although uncommon, does occasionally occur and its possibility should be investigated; a MIBI SPECT study may prove useful in this regard.

Cerebral and Cerebellar Glial Tumors in the Same Individual

We report histologically different gliomas occurring simultaneously in both the cerebrum and cerebellum in a 53-year-old woman. One tumor was a cerebellar astrocytoma, and the second was a temporal glioblastoma multiforme. Two months after the removal of both tumors, the third lesion, located in the basal ganglia, was found on a computed tomographic examination, but it was not verified histologically. We recommend a biopsy of one tumor when a diagnosis of multiple brain tumors is established based on a computed tomographic examination, in order to avoid the misdiagnosis of multicentric gliomas as brain metastases.

Optic Nerve Decompression

Decompression of the perioptic meninges for intractable chronic papilledema was done in a patient with a right parietal temporal glioblastoma multiforme. The patient died 39 days postoperatively. Histologic study of the optic nerves indicated fistulas in the dura compatible with cerebrospinal fluid (CSF) egress and maintenance of a normal subarachnoid space around the nerve. Two additional patients with unilateral optic nerve decompression producing bilateral resolution of papilledema were studied. We contend that egress of CSF was the principle mode of action in these three cases. How long the dural fistula remains patent is unknown. Reports in the literature show considerable variation in the effects of optic nerve decompression. Anatomic variation of the intracanalicular subarachnoid space together with differences in underlying pathologic condition, surgical technique, and patient response may explain discrepancies among the results reported.