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Spectrum of [18F]FDG PET/CT Findings in Primary Central Nervous System Lymphoma – A Pictorial Essay
Address for correspondence: Dr. Tekchand Kalawat, Department of Nuclear Medicine, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India. E-mail: kalawat.svims@gmail.com
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This article was originally published by Wolters Kluwer - Medknow and was migrated to Scientific Scholar after the change of Publisher.
Abstract
Primary central nervous system lymphoma (PCNSL) is a rare, aggressive variant of extranodal non-Hodgkin’s lymphoma. Although gadolinium-enhanced magnetic resonance imaging remains the initial imaging modality of choice, a whole-body F-18 fluorodeoxyglucose (FDG) positron emission tomography–computed tomography is imperative to exclude systemic lymphomatous involvement. Furthermore, the metabolic parameter, maximum standardized uptake value (SUVmax) of the lesion, tumor-to-normal cerebral tissue SUVmax ratio, and FDG uptake patterns help in differentiating intracranial lymphomas from High-grade Glioblastoma Multiforme (HGM) and infectious lesions, and hence, consolidating the diagnosis. In this pictorial essay, we present a series of PCNSL cases, representing the different imaging characteristics and metabolic uptake patterns.
Keywords
F-18 fluorodeoxyglucose positron emission tomography-computed tomography
non-Hodgkin’s lymphoma
primary central nervous system lymphoma
tumor to normal cerebral tissue maximum standardized uptake value ratio
Introduction
Primary central nervous system lymphoma (PCNSL) is the exclusive lymphomatous involvement of the brain, spinal cord, cerebrospinal fluid (CSF), leptomeninges, and vitreoretina.[1] Guidelines established by the International PCNSL Collaborative Group suggest an initial imaging evaluation with gadolinium-enhanced magnetic resonance imaging (MRI), followed by CSF studies, human immunodeficiency viral serology, ophthalmological examination with slit lamp, followed by staging evaluation with computed tomography (CT) chest, abdomen, and pelvis, bone marrow aspiration, and testicular ultrasonography.[2] Although the primary role of F-18 fluorodeoxyglucose positron emission tomography-CT (FDG PET-CT) lies in excluding systemic involvement, metabolic imaging characteristics and parameters also provide additional diagnostic information. This pictorial essay is a compilation of spectrum of F-18 FDG PET-CT findings in PCNSL.
Case 1
A 38-year-old male was evaluated with an MRI brain for complaints of unilateral headache, which revealed an enhancing left frontal lesion with mass effect. Later, a left frontal parasagittal craniotomy and decompression was performed. Postoperative histopathological examination (HPE) was suggestive of lymphoproliferative disorder and immunohistochemistry (IHC) was suggestive of diffuse large B-cell lymphoma (DLBCL), with an MIB-1 index of 95%. The ophthalmic examination was normal. CSF cytology was normal. A whole-body F-18 FDG PET-CT showed intensely avid multiple iso-to-hyperdense lesions in the left frontal lobe, in the region of genu and body of corpus callosum, causing significant perilesional edema and another similar lesion in the left cerebellum [Figure 1]. Received eight cycles of R (rituximab) – methotrexate (MTX), procarbazine, and vincristine regimen, followed by whole brain radiotherapy (WBRT).
Learning point
In the case of PCNSL, the main role of F-18 FDG PET-CT is to rule out systemic involvement. Although the current NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for evaluation of PCNSL, recommends either a whole-body CT with bone marrow biopsy or a F-18 FDG PET-CT for staging evaluation, in a meta-analysis by Park et al., in 2020, concluded that F-18 FDG PET-CT had better diagnostic yield when compared to whole-body CT.[34]
The tumor demonstrates hypercellularity with high nuclear/cytoplasmic ratio, thus it is characterized by intense tumoral FDG uptake. The FDG uptake is more homogenous as the tumor is rarely associated with hemorrhage, necrosis, or calcifications.[5] A study published in 2011 by Makino et al. demonstrated that a maximum standardized uptake value (SUVmax) of >12 helps in differentiating PCNSL from other neoplastic lesions such as high-grade glioblastoma multiforme, with a sensitivity of 100% and specificity of 71.4%.[6] In another study, Kawai et al., put forth a semiquantitative analysis, where the SUVmax of PCNSL lesion is on average 2.5 times greater than that of contralateral normal gray matter.[7] The high FDG avidity of PCNSL lesions may provide useful diagnostic information in differentiating it from High grade Glioblastoma Multiforme (HGM) and infectious lesions. This case demonstrates a typical PCNSL with hyperdense lesions confined to CNS, that are intensely FDG avid, with max. SUV of 25.0 and tumor-to-normal (T/N) ratio of 2.55. The lesion is associated with disproportionate perilesional edema due to compression of blood vessels.
Case 2
A 35-year-old male, a known case of IgA nephropathy, postrenal transplant, and on immunosuppressant therapy for 2 years, presented with complaints of headache. MRI brain showed enhancing altered signal intensity lesions in the right frontal lobe and cerebellum. Subsequently, an F-18 FDG PET-CT was performed, which showed two hyperdense lesions with few central hypodense areas in the right frontal lobe and cerebellum [Figure 2]. Later, the patient underwent craniotomy and tumor excision of the right frontal lobe lesion, and postoperative HPE and IHC were suggestive of DLBCL.
Learning point
The incidence of PCNSL in posttransplant patients, under immunosuppressant therapy, is estimated to be around 7%. In patients with immunocompromised status, PCNSL has an atypical presentation, characterized by multifocal heterogeneous lesions, frequently associated with necrosis or hemorrhage.[8] Due to the atypical characteristics, the FDG uptake is lower compared to typical PCNSL lesions. Similarly, in this case, the SUVmax of the frontal lesion is 8.57 and that of the cerebellar lesion is 10.39, with a T/N ratio of 1.8.
A study conducted by Hustinx et al. concluded that apart from atypical radiographic features, other factors such as corticosteroid use, patient’s plasma glucose level, associated inflammation, and age of the patient may also lead to variations in SUVmax value in primary brain tumors. Hence, F-18 FDG PET-CT should always be reported with caution.[9]
Case 3
A 64-year-old male presented with headache not relieving on medication. MRI brain showed enhancing altered signal intensity lesion in the interventricular region. Subsequently, a right parietal craniotomy and excision of the tumor were performed and postoperative HPE and IHC were suggestive of DLBCL. A whole-body F-18 FDG PET-CT was performed, which showed two intensely FDG avid hyperdense lesions in the interventricular region and left frontal lobe [Figure 3].
Learning point
Usual sites of involvement include frontal lobes (20%–43%), basal ganglia (13%–20%), brainstem and/or cerebellum (9%–13%), and infrequently in the spinal cord (1%–2%).[5]
This case represents a rare site of involvement in the brain, located in the interventricular region extending into the posterior horn of both lateral ventricles.
Case 4
A 61-year-old female was initially evaluated for complaints of inability to recognize persons, behavioral change, headache, and urinary incontinence. MRI brain with contrast showed heterogeneous enhancing lesion involving bilateral frontal lobes, raising a suspicion of glioma. A whole-body F-18 FDG PET-CT showed FDG avid heterogeneous density lesion in bilateral cerebral parenchyma [Figure 4]. A differential diagnosis of Glioma and PCNSL was made. Burr hole and excision biopsy of tumor, with subsequent HPE and IHC, showed evidence of DLBCL. The patient received six cycles of single-agent rituximab and high-dose MTX.
Learning point
One of the classical imaging findings of PCNSL is the “butterfly pattern” or “mirror image.” The lesion symmetrically involves white matter of both hemispheres, usually the frontal lobes, by crossing the midline, through the corpus callosum, which is illustrated in this case. However, it is not specific to PCNSL, as high-grade gliomas also exhibit a similar pattern of brain parenchymal involvement.[10]
Case 5
A 77-year-old female, with a history of hypertension and hypothyroidism, presented with a history of excessive sleepiness, bladder and bowel incontinence, hypnopompic hallucinations, and weakness of left upper and lower limbs. MRI brain showed enhancing lesions in the right frontal lobe, right thalamus, midbrain with optic nerve sheath enhancement, and possible diagnoses included demyelination – neuromyelitis optica and vasculitis. The patient improved symptomatically after treatment with methylprednisolone and a repeat MRI showed reduction of all lesions. Three months after treatment with steroids, the patient again presented with similar complaints. MRI brain showed nodular lesions in the periventricular location of the bilateral frontal region, right thalamus, and septum pellucidum of the brain stem. A whole-body F-18 FDG PET-CT showed intensely avid lesions in the left anterior periventricular white matter and right thalamus and a provisional diagnosis of lymphoma was made [Figure 5]. Subsequently, a right craniotomy and excision of the frontal lesion was performed and postoperative HPE and IHC were suggestive of DLBCL.
Learning point
It is common for PCNSL to present initially as inflammatory demyelinating lesions, with similar disease course and response to corticosteroids. Thus, adding to the difficulty in diagnosis during the initial stages. These multifocal, steroid-responsive lesions mimicking demyelination, are termed “sentinel lesions,” which may undergo malignant transformation in the due course to form lymphomatous lesions. Certain features which should raise the clinical suspicion of PCNSL, include advanced age, disproportionate perilesional edema, worsening of symptoms, and radiographic features of lesion despite adequate treatment with corticosteroids and the absence of spinal cord involvement. Demyelinating lesions show a relatively lower FDG uptake on F-18 FDG PET-CT, which can potentially differentiate it from lymphomatous lesions.[1112]
The lesions on F-18 FDG PET-CT showed a high FDG avidity, with SUVmax of 26.7, thereby making PCNSL the probable differential. As the lesion is located in the right thalamus, diffuse areas of hypometabolism are noted in the right cerebrum and left cerebellar hemisphere, delineating the corticospinal tract.
Case 6
A 43-year-old male presented with progressive weakness of the bilateral lower limbs, associated with paraesthesia, and urinary and fecal incontinence. He reported a history of fall from his bike, 2 weeks prior to the onset of symptoms. He was initially evaluated with an MRI spine which showed clumped and thickened nerve roots of cauda equina with homogenous postcontrast enhancement. A possibility of ependymoma was considered. The patient underwent L1-S1 laminectomy and decompression. Postoperative HPE was suggestive of lymphoproliferative disorder and IHC showed positive for LCA and CD 20 and a diagnosis of high-grade B-cell lymphoma was made. F-18 FDG PET-CT was performed that showed a metabolically active ill-defined soft-tissue density lesion in the spinal canal extending from D-10 to S2 vertebral levels [Figure 6]. Received six cycles of rituximab (R) – cyclophosphamide, doxorubicin, vincristine, prednisolone regimen, and with high-dose MTX, followed by involved site radiation therapy.
Learning point
Neurolymphomatosis is an infrequent manifestation of extranodal non-Hodgkin’s lymphoma, characterized by infiltration of nerves by lymphomatous cells, which include spinal nerve roots, nerve plexus, cranial, and peripheral nerves. As the predominant subtype is DLBCL, F-18 FDG PET-CT serves as a good diagnostic tool, with a sensitivity of 87.5%. This is a case of neurolymphomatosis involving the nerve roots of cauda equina.[13]
Case 7
A 57-year-old female, known diabetic, developed acute-onset memory disturbances and was evaluated with a MRI brain plain study, which revealed a space-occupying lesion in the left frontal lobe with perilesional vasogenic edema and MR spectroscopy showed elevated choline, reduced NAA, and increased choline–creatinine ratio, which was suggestive of neoplastic origin. The patient later underwent craniotomy and lesion excision. Postoperative HPE showed evidence of DLBCL. A F-18 FDG PET-CT was performed for staging evaluation, which revealed an intensely avid hyperdense lesion involving the left frontal lobe and anterior body of the left corpus callosum, with disproportionate perilesional edema [Figure 7]. Received six cycles of rituximab and high-dose MTX and later underwent posttreatment follow-up with F-18 FDG PET-CT. The scan revealed non-FDG avid diffuse gliotic changes in the left frontal lobe region, suggestive of complete response.
Case 8
A 44-year-old male, known case of PCNSL of DLBCL type, received treatment with six cycles of rituximab + high-dose MTX, followed by WBRT. A F-18 FDG PET-CT and Tc-99 m glucoheptonate (GHA) (Tc-99 m GHA) fused single photon emission CT was done for evaluating disease status, that showed a mildly FDG avid and GHA avid lesion in the splenium of the right corpus callosum, which is indicative residual lesion [Figure 8].
Conclusion
The primary role of F-18 FDG PET-CT in PCNSL is to exclude systemic involvement. However, parameters such as SUVmax and T/N ratio help in increasing the sensitivity of diagnosis. Moreover, in cases with atypical presentation and radiographic features, F-18 FDG PET-CT helps in consolidating the diagnosis and management.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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