Leptomeningeal metastases: can MRI compare with CSF analysis

Leptomeningeal metastases: can MRI compare with CSF analysis Poster No.: C-1487 Congress: ECR 2015 Type: Scientific Exhibit Authors: S. GV, S. Juvekar, A. Rastogi, A. Janu, M. Thakur, H. Menon, A. Moiyadi; Mumbai/IN Keywords: DOI: Metastases, Diagnostic procedure, MR, Oncology, Neuroradiology brain, Neoplasia 10.1594/ecr2015/C-1487 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. www.myesr.org Page 1 of 16

Aims and objectives Aims and objectives: Leptomeningeal metastasis (LMM) is one of the frequent form of CNS involvement by systemic cancer. Due to improvement in the diagnostic modalities and increase of survival rates due to advancement in the treatment in oncology, the incidence of leptomeningeal metastasis is increasing. Prognosis remains poor in these patients. Aim of the study is to demonstrate diagnostic accuracy of neuroimaging in patients with non-cns primary malignancies having signs and symptoms of leptomeningeal disease. Introduction: CNS metastases are broadly divided into parenchymal and extra-axial metastasis. Extra-axial includes skull, dural or leptomeningeal spread [1]. Leptomeningeal invasion gives rise to tumor cell dissemination by the cerebrospinal fluid. Several hypotheses have been proposed for pathophysiology of the Leptomeningeal metastases including haematogenous [2], perineural [3] or perivascular and direct spread. Demonstration of the metastatic cancer cells in the CSF has been considered as gold standard within the limitation of its low sensitivity [4]. This necessitates repeat CSF analysis to increase detection rate. The CSF typically shows elevated proteins and hypoglycorrhachia (low sugar in CSF), supporting the cytological evidence. Other diagnostic modalities includes MR imaging of brain & spine, CECT brain, 111Indium-DTPA Radionucleotide CSF #ow studies, 18-FDG PET and 11C-Methionine PET scan. Meningeal biopsy is considered when the diagnosis remains uncertain and other causes of chronic meningitis have been excluded [5, 6]. Among the imaging studies, MRI is superior over other modalities in detection of the pathologies of meninges. Specifically, contrast-enhanced fast T2 FLAIR imaging is sensitive for the evaluation of leptomeningeal lesions [7]. MRI has emerged as an initial, non-invasive tool for evaluation of LMM, with improved visualization of subarachnoid space and development of new sequences like contrast-enhanced T2 FLAIR [8]. Images for this section: Page 2 of 16

Fig. 1: Schematic diagram showing calvarial (arrow), epidural (arrow head) and subarachnoid metastasis (asterisk). Page 3 of 16

Methods and materials The patients with clinical features of LMM and those who underwent both MRI brain/spine and CSF analysis were considered for analysis. Patients with parenchymal metastasis were excluded from the study. Patients who underwent < 3 CSF study which are negative are not included in the study to reduce confounding. 36 patients (14 males and 22 females of age group ranging from 14 to 74 years) with known non CNS cancer who presented with clinical features of leptomeningeal involvement from Jan 2011 to Dec 2013 were analyzed. The patients were identified through PACS and HIS database. The potential cases of leptomeningeal metastasis underwent both MR imaging and CSF analysis. Data obtained included patient age, gender, primary cancer and its histology as well as MRI and CSF analysis. The MRI parameters as follows: Performed on 1.5 tesla (T) GE Signa.HDxt MRI machine, from base of skull to vertex. The routine sequences includes axial T1, Axial T2, axial FLAIR, post contrast axial, coronal and sagittal images for brain and sagittal T1, T2 and post contrast sequences for spine, axial images were also obtained in the area of interest. As this is a retrospective study, few of the patients have not got contrast-enhanced FLAIR images. However LMM is easily visualized on contrast-enhanced FLAIR images than on contrast-enhanced T1-weighted images because FLAIR imaging slightly suppresses the cortical vein signals. Recent sequences modification also includes chemical fat saturation along with fluid suppression in the post contrast images [8, 9]. MR morphology for diagnosing LMM were 1. Linear enhancement along the cisterna, sulci or dura 2. Cranial nerve enhancement 3. Enhancing nodules in cisterna or subarachnoid space of spine 4. Communicating hydrocephalus with other causes being ruled out CSF was considered positive if cytology showing malignant cells. Page 4 of 16

Both MRI and CSF results were made into nominal binary values (positive or negative) for statistical analysis. Statistical analysis: Data was analyzed with SPSS Statistics software. This includes the descriptive analysis of gender, age distribution and primary malignancy. Sensitivity, specificity, and negative and positive predictive values of MRI were determined by taking CSF analysis as reference standard. Single CSF cytology is not a gold standard test in diagnosis of LMM, with specificity of 95% [10, 11] and with repeated lumbar puncture sampling the sensitivity reaches up to 90% [10, 12]. In this study, 3 consecutive negative analysis was taken as negative. Images for this section: Page 5 of 16

Fig. 2: Case of Ca ovary, MRI showing linear enhancement along the perisylvian meninges. Page 6 of 16

Fig. 3: Case of melanoma with leptomeningeal metastasis and communication hydrocephalus. Page 7 of 16

Fig. 4: Case of Ca breast with leptomeningeal metastases with parenchymal extension. Page 8 of 16

Fig. 5: Sagittal image of dorsal spine showing linear and nodular enhancement along posterior aspect of the spinal cord. Page 9 of 16

Results A total of 36 patients with potential LMM underwent both MRI and CSF analysis, 20 cases were positive for leptomeningeal disease on MRI. Of these patients, 16 showed positive CSF cytology whereas 4 patients had CSF samples negative for malignant cells. Out of 16 patients with negative MRI findings, only 3 were positive on CSF cytology and rest 13 were negative in CSF cytology also. The median age of presentation was 47.5 years. MRI CSF Cross tabulation: MRI CSF Positive Negative Total Positive 16 4 20 Negative 3 13 16 Total 19 17 36 The calculated values were as follows Sensitivity: 84.21 % if 95% CI: 60.40 % to 96.43 % Specificity: 76.47 % if 95% CI: 50.10 % to 93.04 % Positive Predictive Value: 80.00 % Negative Predictive Value: 81.25 % Positive Likelihood Ratio: 3.58 Negative Likelihood Ratio: 0.21 Fisher's exact test and Chi-Square tests: Value df Asymp.Sig Exact Sig Exact Sig Pearson Chi-Squre (2 sided) 13.380 1 0.000 (2 sided) (1 sided) Page 10 of 16

Continuity Correction Likelyhood Ratio 1 0.001 1 0.000 Fisher's Exact Test 0.001 0.000 N value of valid cases 36 The smallest value in the table is less than 5, so Fisher's exact test was applied. Strength and weakness of study: Strength: Patient selection was unbiased. Every patient has got histological diagnosis. In every suspected LMM, infection was ruled out. No confounding factors like previous brain surgery were identified. Weakness: In our institute, not all the patients underwent both CSF and MRI on the basis of clinical features. Few are diagnosed with CSF alone or MRI alone. This was limiting number of cases available for analysis. Additional parameters (opening pressure, proteins and glucose values in CSF and recent developing biomarkers) of CSF analyses are not included along with the CSF cytology. Images for this section: Page 11 of 16

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Conclusion LMM is a clinically important neurological complication of systemic malignancy and is increasingly appearing in frequency. Demonstration of tumor cells in CSF is specific for LMM, however CSF analysis has its own limitations like low sensitivity, invasiveness and risk of complications in patients with elevated intracranial pressure. The diagnostic accuracy of MRI is comparable with CSF analysis with use of Gd contrast and with newer techniques like post contrast FLAIR. With typical clinical features and diagnostic features of neuroimaging leptomeningeal metastasis can be diagnosed in absence of CSF study or if negative. Personal information SanthoshKumar GV, post graduate student, Department of radio diagnosis, Tata Memorial Hospital, Mumbai, India; gvsanthoshbmc@gmail.com Shashikant Juvekar, Professor, Department of radio diagnosis, Tata Memorial Hospital, Mumbai, India; sljuvekar@gmail.com Ashita Rastogi, Fellow in Onco-Radiology, Department of radio diagnosis, Tata Memorial Hospital, Mumbai, India; ashitarastogi@hotmail.com Amit Janu, Assistant Professor, Department of radio diagnosis, Tata Memorial Hospital, Mumbai, India; amiteasy10@gmail.com Meenakshi Thakur, Professor and head of the department, Department of radio diagnosis, Tata Memorial Hospital, Mumbai, India; thakurmh@yahoo.co.in Hari Menon, Associate Professor, Department of medical oncology, Tata Memorial Hospital, Mumbai, India; menontata@yahoo.in Aliasgar Moiyadi, Associate Professor, Department of neurosurgery, Tata Memorial Hospital, Mumbai, India; amoiyadi@actrec.gov.in Page 15 of 16

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