Radiology Case Reports 16 (2021) 72–77 Available online at www.sciencedirect.com journal homepage: www.elsevier.com/locate/radcr Case Report MR imaging findings in primary spinal cord glioblastoma ✩ Paolo Ferrante, MDa,b, Juan Andres Mora, MDb,c, Lourdes Salazar, MDd, Elena Martínez Sáez, MDd, Cristina Auger, MDb,e, Àlex Rovira, MDb,e,f,∗ a Diagnostica per Immagini e Radiologia Interventistica, Policlinico Tor Vergata, University Rome “Tor Vergata”, Rome, Italy b Section of Neuroradiology, Department of Radiology, Vall d’Hebron University Hospital, Hospital Vall d’Hebron, Passeig de la Vall d’Hebron, 119-129 | 08035, Barcelona, Spain c Fundación Universitaria Sanitas, Clinica Reina Sofia, Bogotá, Colombia d Neuropathology Unit, Pathology Department, Vall d’Hebron University Hospital, Hospital Vall d’Hebron. Barcelona, Spain e Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron University Hospital, Barcelona, Spain f Universitat Autònoma de Barcelona, Bellaterra, Spain a r t i c l e i n f o a b s t r a c t Article history: Spinal cord glioblastoma is a rare disease, with an aggressive course and a poor progno- Received 24 August 2020 sis. We describe magnetic resonance imaging (MRI) findings, in 3 adult cases of biopsy- Revised 19 October 2020 confirmed glioblastoma. Accepted 23 October 2020 Conventional MRI findings were unclear with regard to the differential diagnosis be- tween this rare tumor and other more common spinal cord lesions, including less aggressive tumors such as ependymoma or pilocytic astrocytoma, abscesses or tumefactive demyeli- Keywords: nating lesions. After reasonable exclusion of infectious/inflammatory conditions, a final di- Spinal cord glioblastoma agnosis of glioblastoma was established based on histopathological analysis. The cases re- Primary spinal cord tumors ported reflect the difficulty of early radiological diagnosis of spinal cord glioblastoma, and Glial tumors indicate the need to perform a biopsy once inflammatory-infectious conditions are excluded MRI with appropriate laboratory tests. © 2020 Published by Elsevier Inc. on behalf of University of Washington. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) cases reported in the medical literature [1]. This tumor ac- Introduction counts for approximately 7.5% of all intramedullary gliomas and 1.5% of all spinal cord tumors [1]. It has a highly aggressive Although glioblastoma (GB) is the most common primary ma- course with a very poor prognosis due to its infiltrative growth lignant tumor of the central nervous system (CNS), their loca- and the impossibility of complete surgical resection. Median tion in the spinal cord is extremely rare with less than 200 survival rate is approximately 14 months, even in the setting ✩ Declaration of competing interest: None. ∗ Corresponding author. E-mail address: alex.rovira.idi@gencat.cat (À. Rovira). https://doi.org/10.1016/j.radcr.2020.10.043 1930-0433/© 2020 Published by Elsevier Inc. on behalf of University of Washington. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) Radiology Case Reports 16 (2021) 72–77 73 Fig. 1 – Spinal cord MRI from patient 1. Sagittal T1-weighted image shows an iso- to hypointense mass in the cervical cord (A). The lesion is better demarcated on the sagittal T2-weighted sequence (B). An intense peripheral enhancement is shown on the contrast enhanced axial and sagittal T1-weighted images (C-F). Observe the exophytic component of the lesion in its upper portion on the right side (arrows in E and F). of aggressive multimodality treatment [2]. The highest inci- dence is between the second and third decade of life [2], and the most common location is the cervical and thoracic spinal cord. Less commonly, it can occur in the conus medullaris [3]. Due to its rarity, spinal cord GB might be misdiagnosed ra- diologically with infectious and inflammatory conditions, or with less malignant and more common types of spinal cord tumors. We report 3 cases of spinal cord GB, analyze the imag- ing features, and discuss differential diagnoses of this rare disease. Case 1 A 34-year-old woman with a history of neurofibromatosis type 1 (NF1), presented to the emergency department with motor weakness of the right arm and sensory disturbances Fig. 2 – Histological images from patient 1, showing a of the lower limbs that started 4 days before admission. The hypercellular proliferation composed of round-to-oval patient had no fever or systemic symptoms, and no previous medium-sized nuclei, with foci of necrosis (A. hematoxylin history of cancer or trauma. On neurological examination, the and eosin stains, 200×), with strong and diffuse GFAP patient showed paraparesis and hypoesthesia of the upper expression (B, 200×). Absence of IDH1 R132H mutation (C, extremities and general hyper-reflexia of the lower limbs. A 200×, with positive control in the inset), absence of ATRX cervical spine MRI showed an extensive intraspinal - intradu- expression with positive internal control, consistent with ral infiltrative expansile lesion with an exophytic component, ATRX mutation (D, 200×), absence of p53 overexpression (E, which involved nearly the entire cervical spinal cord, and 200×). extended cranially to the lower part of the medulla oblongata including the area postrema (Fig. 1). The lesion showed a homogeneous peripheral and eccentric enhancement of both the intramedullary and exophytic components of the found on histological analysis. Two mitoses were identified lesion at its proximal segment (Fig. 1). Brain MRI showed in the whole material, with frequent foci of necrosis and only bilateral subcutaneous epicranial lesions in the occipital endothelial hyperplasia. The neoplastic cells expressed glial regions, compatible with neurofibromas, and a left parotid fibrillary acidic protein (GFAP), with loss of ATRX expression. lesion suggestive of a plexiform neurofibroma. Oligoclonal No isocitrate dehydrogenase (IDH), BRAF nor H3 K27M muta- bands in CSF and serum antibodies to aquaporin-4 (AQP4-Ab) tions were found and no p53 overexpression was seen. The were negative. A spinal cord biopsy was performed, and a proliferation index (measured by Ki67) reached 7%. These highly cellular lesion composed of medium-sized, oval nuclei findings were consistent with a grade IV, IDH-wild type GB with granular chromatin and eosinophilic cytoplasm was (WHO 2016) (Fig. 2). Due to the location and histopathology 74 Radiology Case Reports 16 (2021) 72–77 Fig. 3 – Spinal cord MRI from patient 2. Sagittal T1-weighted image shows an iso- to hypointense mass in the conus medullaris (A). The lesion is better demarcated on the sagittal T2-weighted sequence (B). An intense peripheral enhancement delimiting a central area of necrosis associated with an eccentric enhancing nodule (arrow in C) is shown on the contrast-enhanced sagittal and axial T1-weighted images (C and D). of the tumor, and the rapid clinical deterioration, it was decided not to perform any treatment. The patient developed hydrocephalus and passed away 2 months after admission, most likely to rapid disease progression. Case 2 A 64-year-old man without any past medical history presented to the emergency department after a 3-week history of mo- tor weakness of the lower extremities with associated sensory disturbances. Neurological examination showed paraparesis and decreased sensation in the anterior region of both thighs and in the genital and the perianal areas. There were no neu- rologic abnormalities of the upper limbs and cranial nerves and no sphincter dysfunction. A lumbar spine MRI revealed an ovoid, intramedullary, expansile lesion involving the conus Fig. 4 – Histological images from patient 2 (hematoxylin medullaris with homogeneous hyperintense signal inten- and eosin stains, 200×). The sample shows hypercellular sity on T2-weighted images. After injection of contrast, the le- proliferation composed of oval medium-sized nuclei, with sion demonstrated an irregular, thick peripheral enhance- mitotic activity and endothelial hyperplasia. ment, delineating a central area of necrosis associated with an eccentric enhancing nodule (Fig. 3). These imaging features were consistent with a spinal cord tumor, although an infec- tious lesion was also considered. Serological testing for dif- Case 3 ferent infectious diseases including Toxoplasma gondiiwas all negative. The patient was surgically treated with partial re- A 47-year-old patient with a history of hyperuricemia and ar- section of the lesion. Histologically, a moderately cellular le- terial hypertension presented to the hospital with 18 months sion composed of medium-sized, oval, hyperchromatic nuclei history of progressive spinal cord symptoms with paresthe- with scant cytoplasm was identified, with a prominent myx- sia in the lower right extremity starting in the foot and as- oid background (Fig. 4). Mitotic activity reached 5 mitoses/10 cending to the leg, accompanied by episodes of intense pain, high power fields, with necrosis and vascular proliferation. loss of thermic sensitivity, and numbness of left arm. A cer- The neoplastic cells expressed GFAP and preserved ATRX ex- vicothoracic spine MRI was performed in another institution pression. No IDH mutations, epidermal growth factor recep- that showed 2 tumefactive intramedullary lesions involving tor (EGFR) amplification nor BRAF translocation were found. the cervical and thoracic segments. A diagnosis of tumefac- P53 expression reached 40%. The proliferation index (mea- tive inflammatory lesions was initially suggested and the pa- sured by Ki67) reached 30%. These findings were consistent tient was treated with corticosteroids, without clinical im- with a grade IV, IDH-wild type GB (WHO 2016). The patients provement. Oligoclonal bands in CSF and serum antibodies started treatment with radiotherapy and chemotherapy, but to aquaporin-4 (AQP4-Ab) and myelin oligodendrocyte glyco- recurrent disease was demonstrated 13 months later, and he protein (MOG) were negative. The patient clinically progressed passed away 20 months after his initial diagnosis. over the next 4 weeks, developing motor weakness of his left Radiology Case Reports 16 (2021) 72–77 75 These findings were consistent with a grade IV, IDH-wild type GB (WHO 2016). The patient was treated with radiotherapy and chemotherapy but rapidly progressed clinically and ra- diologically and passed away 10 months after first hospital admission. Discussion Glioblastoma is the most frequent malignant tumor of the CNS, and constitutes 12%-15% of all intracranial neoplasms [4], but it is a rare entity in the spinal cord, with only less than 200 cases reported in the literature [1]. Spinal cord GB has a Fig. 5. – Spinal cord MRI from patient 3. Sagittal STIR image predilection to develop from the cervical cord segment and shows multifocal lesion that affects the cervical (C5-C7) and has a tendency to develop at a younger age compared to those dorsal (D3-D5) spinal cord segments (A). Contrast-enhanced primarily involving the brain [5]. sagittal and axial T1-weighted images (B-E) demonstrates Histopathologically, spinal cord and brain GB are identical. peripheral enhancement and a small necrotic center However, there is no molecular marker specific for spinal cord (arrows). GB and markers such as IDH-1 and O6-methylguanine-DNA methyltransferase promoter methylation only have prognos- tic significance for supratentorial GBs [6]. Its location at the cervical spinal cords segment is more fre- quent and clinical symptoms depend on the degree of spinal cord damage [7]. These tumors frequently show contiguous dissemination, and through cerebrospinal fluid also dissemi- nate to distant sites, which significantly reduce survival [8]. Spinal cord MRI is considered the gold standard imaging modality to diagnose spinal intramedullary tumors, although differentiation of primary spinal cord GB from other spinal cord diseases, such as infectious and inflammatory disorders, or other intramedullary tumors, is challenging, since primary spinal cord GBs show MRI features that are similar to these conditions (intramedullary longitudinally extensive lesions with patchy heterogeneous enhancement and intralesional cysts or necrosis). Therefore, a definitive diagnosis requires tissue biopsy and histopathological evaluation. The majority of primary spinal cord GBs appear as infiltrative expansive masses with iso or low signal on T1-weighted, and high signal on T2-weighted images, and heterogeneous enhancement on Fig. 6 – Histological images from patient 3 (hematoxylin contrast-enhanced T1-weighted images [1]. Nonconventional and eosin stains, 200×). Observe the hypercellular MRI sequences could provide additional useful features, proliferation composed of large and medium-sized nuclei, such decrease in fractional anisotropy on diffusion tensor multinucleated cells, and atypical mitoses, with endothelial images that correlates with the severity of infiltration and hyperplasia. destruction of spinal nerve tissue [9] and increase in relative blood volume (>1.8) on dynamic susceptibility contrast MRI perfusion caused by the angiogenesis that characterized arm, and came to our institution for a more extensive diag- these tumors [9]. nostic work-up. A new cervicothoracic spine MRI revealed 2 In the first patient, the lesion had an exophytic exten- fusiform expanding lesions involving the C5-C7 and T3-T5 sion, defined as the growth of tumor beyond the pia mater spinal cord segments, with contrast-uptake delineating cen- and into the subarachnoid space, which has been previously tral areas of necrosis (Fig. 5). A spinal cord biopsy was per- described in spinal cord GB [10]. In this case, the initial dif- formed on the cervical cord lesion, which showed a highly ferential diagnosis included, in addition to GB, pilocytic as- cellular tumor, composed of large and irregular nuclei, with trocytoma, ependymoma, and neuromyelitis optica spectrum frequent bizarre and multinucleated cells, and a high mi- disorder (NMOSD). Pilocytic astrocytoma is the most common totic index (reaching 13/10 high power fields). Frequent im- intramedullary tumor in patients with NF1 [11], and mainly ages of vascular proliferation and necrosis were found (Fig. 6). involves the cervical segment arising eccentrically within the The neoplastic cells expressed GFAP. No p53 overexpression, cord. Additional imaging features are a cystic mass with a EGFR amplification nor IDH and BRAF mutations were present. mural nodule showing a diffuse nonhomogeneous contrast The proliferation index (measured by Ki67) reached 65%. enhancement [12]. Ependymomas have been also described 76 Radiology Case Reports 16 (2021) 72–77 as associated with NF-1, but we could not find in the medi- to confirm this diagnosis, after reasonable exclusion of infec- cal literature and association between NF-1 and GB. NMOSD tious and inflammatory conditions through appropriate labo- was considered in the differential diagnosis, as the lesion ex- ratory tests. tended to the area postrema in the lower part of the brainstem, an MRI feature initially considered to be specific to NMOSD, but later seen in other conditions associated with longitudi- nally extensive cervical cord lesions [13]. Also, the presence Patients Consent Statement of the exophytic component suggested this diagnosis, as lep- tomeningeal enhancement has been described in this condi- Written informed consent could not be obtained from the pa- tion [14] However, this diagnosis was excluded as AQP4 anti- tients as they all were exitus few months after diagnosis. All bodies were not detected and there was no additional clinical the images included in this Case report are entirely unidentifi- involvement beside the spinal cord, which is a requirement able and there are no personal details on individuals reported to establish this diagnosis according to the 2015 NMOSD diag- nostic criteria [15]. The second case was a GB located in the conus medullaris, REFERENCES which is a very rare location for this tumor. A retrospective study that collected 128 cases from 1938 to 2015, showed that 42.2% of spinal cord GBs were located in the thoracic spine, [1] Shen CX, Wu JF, Zhao W, Cai ZW, Cai RZ, Chen CM. Primary 29.7% in the cervical spine, while those located in the conus spinal glioblastoma multiforme: a case report and review of level only accounted for 14% of cases [3,4]. In fact, we did not the literature. 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