Diagnostic Performance of Baseline 18F-Fluoro-Deoxy- Glucose Positron Emission Tomography/Computed Tomography in Patients with Clinico-Radiological Suspicion of Primary Central Nervous System Lymphoma

Rapid Communication

Ann Hematol Oncol. 2019; 6(1): 1228.

Diagnostic Performance of Baseline 18F-Fluoro-Deoxy- Glucose Positron Emission Tomography/Computed Tomography in Patients with Clinico-Radiological Suspicion of Primary Central Nervous System Lymphoma

Gupta T¹*, Gupta M¹, Purandare N², Puranik A², Rangarajan V², Moiyadi A³, Shetty P³, Epari S4, Pungavkar S5, Krishnatry R¹, Sastri G¹ and Jalali R¹

1Department of Radiation Oncology, Tata Memorial Centre, India

²Department of Nuclear Medicine & Molecular Imaging, Tata Memorial Centre, India

³Department of Neuro-surgery, Tata Memorial Centre, India

4Department of Pathology, Tata Memorial Centre, India

5Department of Imaging & Radio-diagnosis, Global Hospitals, India

*Corresponding author: Tejpal Gupta, MD, DNB, Professor, Department of Radiation Oncology, ACTREC, Tata Memorial Centre, Homi Bhabha National Institute, Kharghar, Navi Mumbai, India

Received: December 03, 2018; Accepted: January 25, 2019;Published: February 01, 2019


Background: Morphological features of Primary Central Nervous System Lymphoma (PCNSL) have considerable overlap with other common intra-cranial lesions such as high-grade glioma, brain metastasis, and infection/inflammation on Magnetic Resonance Imaging (MRI) rendering pre-operative diagnosis difficult. We hypothesized that significantly higher uptake in PCNSL compared to other lesions on baseline 18F-Flouro-Deoxy-Glucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT) would allow more accurate and reliable diagnosis.

Methods: Adult patients with a differential diagnosis of PCNSL on conventional neuro-imaging underwent pre-biopsy whole-body FDG-PET/CT after written informed consent followed by planned neuro-surgical intervention for confirmation of diagnosis at a single institute. All pre-treatment FDG-PET/ CT scans were reviewed and interpreted independently by a senior imaging specialist in an unbiased manner, who reported the ‘likely’ diagnosis on FDGPET/ CT blinded to final histo-pathology. Diagnostic performance of baseline FDG-PET/CT was calculated using pathological diagnosis as the reference standard.

Results: Twenty-six of 45 patients were diagnosed as having CNS lymphoma (including 3 with systemic lymphoma), while remaining 19 patients were deemed to have ‘non-lymphomatous’ lesions such as high-grade glioma, brain metastasis, infection/inflammation on pre-treatment FDG-PET/CT. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of qualitative FDG-PET/CT with 95% confidence interval (95% CI) in the diagnosis of PCNSL (excluding 3 patients with systemic lymphoma) was 77.4% (95% CI=54.6-92.2%); 70% (95% CI=45.7-88.1%), 73.9% (95% CI=58.3-85.2%), 73.7% (95% CI=55.2-86.4%), and 73.8% (95% CI=58-86.1%) respectively.

Conclusions: Baseline FDG-PET/CT has acceptable diagnostic accuracy (adjunctive to MRI) in suspected PCNSL, particularly in patients with deepseated lesions not amenable to a safe neuro-surgical biopsy.

Keywords: Diagnostic accuracy; Brain; FDG-PET/CT; Lymphoma; MRI


Primary Central Nervous System Lymphoma (PCNSL) is a rare and aggressive form of extra-nodal Non-Hodgkin’s Lymphoma (NHL) that arises in the brain, eyes, leptomeninges, or spinal cord in the absence of systemic lymphoma at index diagnosis [1,2]. Multiparametric contrast-enhanced Magnetic Resonance Imaging (MRI) supplemented with spectroscopy, diffusion, and perfusion techniques is the recommended first-line imaging modality for assessment and characterization of intra-cranial lesions including suspected PCNSL [3]. In immuno-competent adults, lesion(s) of PCNSL are typically located in the deep peri-ventricular white matter, show intense solid contrast enhancement without necrosis, and are associated with restricted diffusion and variable peri-focal edema [3,4]. Although, the above-mentioned imaging characteristics are highly suggestive of PCNSL, they cannot reliably and unequivocally differentiate CNS lymphomas from other lesions such as glioblastoma, metastases, and inflammatory or infectious pathologies which may have similar morphology on conventional neuro-imaging [5,6]. Unlike other brain tumors, such as high-grade gliomas or metastases that need maximal safe neuro-surgical resection, often only a biopsy (stereotactic or open) is required in patients with suspected PCNSL for histopathological confirmation of diagnosis. However, even a small biopsy from lesion(s) located deep in eloquent brain may be associated with significant morbidity or be contraindicated in patients with poor performance status. Thus, there is an unmet need for a non-invasive, reliable, and cost-effective adjunctive imaging modality in the initial diagnostic evaluation of patients with suspected PCNSL.

As a contemporary metabolic imaging modality, 18F-Fluoro- Deoxy-Glucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT) has demonstrated excellent clinical utility in the diagnosis, staging, and response assessment in systemic lymphoma [7,8]. Systemic Diffuse Large B-Cell Lymphoma (DLBCL) is typically associated with very high FDG-uptake that is helpful in differentiating it from other histologic entities. We hypothesized that similar to peripheral lesions in systemic lymphoma, FDG-uptake should be sufficiently and significantly higher in PCNSL (being largely DLBCL) compared to other intra-cranial lesions with similar morphology on conventional neuro-imaging allowing accurate and reliable diagnosis. The aim of our study was to assess the diagnostic performance of baseline whole-body FDG-PET/CT as imaging modality (adjunctive to MRI) in patients with a clinico-radiological suspicion of PCNSL.

Materials and Methods

Adult patients with a differential diagnosis of PCNSL on conventional neuro-imaging (as per discussion in the multidisciplinary neuro-oncology joint clinic) were accrued after written informed consent on a prospective observational imaging study at a single institute from October 2014 till July 2017. All patients underwent baseline (pre-biopsy) whole-body FDG-PET/CT scan. This was followed by a planned neuro-surgical intervention either biopsy (stereotactic or open) or resection as deemed appropriate and safe by the neuro-surgeon to provide confirmatory histo-pathological diagnosis. In patients with deep seated lesions wherein biopsy was considered hazardous, and in patients with obvious leptomeningeal enhancement, Cerebrospinal Fluid (CSF) testing for malignant cell cytology (supplemented with flow-cytometry, as and when necessary) was performed to arrive at a cytological diagnosis. The study was duly approved by the Institutional Ethics Committee that functions in accordance with the Declaration of Helsinki. All FDG-PET/CT scans on the study were supported through a competitive intramural research grant.

FDG-PET/CT imaging: After 6-hours of fasting and confirming normal plasma glucose levels (<150mg/dl), 5MBq/kg body-weight of 18-F-FDG was injected intravenously. Static whole-body images (scan volume extending from skull vertex till mid-thigh) were obtained 45-60 minutes post-injection of the radioisotope on dedicated PET/ CT scanners (Discovery ST, GE Healthcare and Astonish TF, Philips Healthcare). PET images were acquired in three-Dimensional (3D) mode on a Time-of-Flight (TOF) system using approximately 8 bed positions (60-90 seconds per bed position) and 50% overlap for the emission study. PET images were reconstructed iteratively using the Row Action Maximum Likelihood Algorithm (RAMLA). The corresponding CT with 80-100ml of non-ionic intravenous contrast was acquired at 120 kV and set to auto mA as tube current. Attenuation correction of the TOF acquired data was done using post-acquisition correction algorithms. Dead-time correction and decay correction was also applied as appropriate. Region of Interest (ROI) was placed on the tumor using image slices corresponding to maximum FDG-tracer uptake. Maximum Standardized Uptake Value (SUVmax), a commonly used semi-quantitative measure of FDGuptake was expressed as a ratio of the maximum tissue radioactivity concentration ‘c’ of FDG in the selected ROI at time point ‘t’ (MBq/ kg) and decay corrected amount of injected FDG (MBq) divided by patient’s body weight (Kg).

All pre-treatment FDG-PET/CT scans were reviewed and interpreted independently by a senior imaging specialist in an unbiased manner, who reported the ‘likely’ diagnosis on FDG-PET/ CT blinded to the final histo-pathology. The diagnostic performance of baseline FDG-PET/CT was calculated with histological/cytological diagnosis as reference standard using standardized indices including sensitivity, specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV), and overall accuracy along with their 95% Confidence Intervals (95% CI).


A total of 55 patients were consented prior to any neurosurgical biopsy/resection on our prospective observational imaging study assessing the diagnostic performance of pre-treatment FDG-PET/ CT in patients with a clinic-radiological suspicion of PCNSL. One patient withdrew consent and another patient died even prior to PET imaging, leaving 53 patients with baseline whole-body FDG-PET/ CT. Diagnosis was confirmed histologically and/or cytologically in 49 patients (3 patients did not undergo biopsy due to the presence of deep-seated lesions and 1 died shortly after FDG-PET/CT awaiting biopsy confirmation). Three patients who had undergone prebiopsy FDG-PET/CT at an outside centre and one patient with an incidentally detected FDG-avid lung mass on whole-body FDGPET/ CT were excluded from the calculation of metrics of diagnostic accuracy thereby leaving 45 patients that constitute the study cohort. The study work-flow is depicted in (Figure 1), while baseline patient and disease characteristics are described in (Table 1).