Clinical Review & Education
JAMA Oncology Clinical Challenge
Atypical Imaging Findings in an Immunocompetent Patient Julia Savage, MD; Douglas Quint, MD
A
B
Figure. Magnetic resonance images (MRIs) of the head obtained 8 months after patient’s first clinical visit. A, Axial T2-weighted MRI of the head at the level of the lateral ventricles demonstrates extensive ill-defined areas of increasing signal with only minimal associated mass effect involving the frontal lobe white matter, greater on the left than on the right. B, Contrast-enhanced T1-weighted MRI at the same level demonstrates abnormal patchy enhancement of the head of the left caudate nucleus and the deep anterior left frontal lobe white matter.
A previously healthy woman in her 50s presented with complaints of increasing forgetfulness, fatigue, and depressed mood after dealing with the deaths of several close relatives. She was diagnosed with depression and began treatment with antidepressant medication. After 8 months, she had worsening complaints. At that time, a family member reported that her memory problems had progressed. She was no longer able to find misplaced objects, remember appointments, or handle financial affairs. She was often subdued, her mood depressed, and her sleeping time increased. Clinical examination at that time revealed a flattened affect and a 22 of 30 Mini-Mental State Examination score. Findings were otherwise normal, and there were no focal neurologic deficits. Basic laboratory workup results were unremarkable. She was referred to a neurologist, who ordered contrast-enhanced magnetic resonance imaging (MRI) of the brain. The MRI (Figure) revealed extensive ill-defined areas of FLAIR (fluid-attenuated inversion recovery) and T2 signal abnormalities with additional enhancing nodular foci located within deep white matter structures, the basal ganglia, the caudate, the pons, and the midbrain. Also identified was enhancement of the interpeduncular cistern and cerebral peduncles, suggestive of leptomeningeal involvement.
jamaoncology.com
WHAT IS YOUR DIAGNOSIS?
A. Inflammatory demyelinating processes such as multiple sclerosis B. Neoplasms such as multicentric glioma, glioblastoma multiforme, and metastases C. Infectious causes including tuberculosis, neurosyphilis, and toxoplasmosis D. Primary central nervous system lymphoma
(Reprinted) JAMA Oncology May 2015 Volume 1, Number 2
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://oncology.jamanetwork.com/ by a New York University User on 05/27/2015
247
Clinical Review & Education JAMA Oncology Clinical Challenge
Diagnosis D. Primary central nervous system lymphoma
Discussion Following imaging, the patient underwent stereotactic brain biopsy, which revealed diffuse large B-cell lymphoma. Further workup revealed no other sites of disease, and Primary central nervous system lymphoma (PCNSL) was diagnosed. Contrast-enhanced MRI is the preferred imaging technique for evaluating PCNSL because it is useful for staging and biopsy planning (ability to identify spinal and/or leptomeningeal involvement). Histologically, PCNSL demonstrates dense cellular lesions that have the classic appearance of isodense to hyperdense areas on computed tomography scans and isointense to hypointense regions on T1-weighted MRI scans, which are hyperintense to white matter on T2-weighted MRI images. Unlike metastatic lesions, which often have a distinct border with contiguous brain parenchyma, PCNSL often demonstrates an infiltrative pattern within brain parenchyma. These lesions typically exhibit intense, homogeneous enhancement after contrast administration. In a study that looked at MRI features in 100 patients with PCNSL,1 only 1 patient had lesions that did not have strong or moderately strong contrast enhancement. Ring enhancement of the lesions can be seen in cases of PCNSL in immunocompromised individuals, such as those with human immunodeficiency virus (HIV), but such enhancement is considered a rare finding in immunocompetent patients.2 In the same study,1 90 of a subpopulation of 96 patients with PCNSL had significant edema on MRI imaging. Along with contrast enhancement, surrounding edema is another classic finding with PCNSL, which often results in local mass effect. In immunocompetent patients, PCNSL most frequently presents as a single lesion. In some cases, however, it can present as multiple lesions, which is a typical imaging finding in patients with HIV lymphoma. In the review of 100 patients with PCNSL,1 it was found that 65% of patients presented with only 1 lesion. Most frequently involving the cerebral hemispheres, PCNSL can also involve all areas of the craniospinal axis, including brain parenchyma, leptomeninges, spinal cord, and eyes. Within the ARTICLE INFORMATION Author Affiliations: Department of Radiology, University of Michigan Health System, Ann Arbor. Corresponding Author: Julia Savage, MD, Department of Radiology, University of Michigan Health System, 1500 E Medical Center Dr, UH B1G503, Ann Arbor, MI 48109-5030 ([email protected]).
248
brain itself, PCNSL can involve the cortex, deep structures such as basal ganglia, corpus callosum, and periventricular regions.3 Of 100 patients with PCNSL,1 cerebral hemispheric involvement was present in 38% (most commonly in the frontal lobes). The basal ganglia were involved in 16% of cases, corpus callosum in 14%, and periventricular regions in 14%. Leptomeningeal and cerebellar involvement was found to be the least likely location.1 Primary central nervous system lymphoma can also present with ocular involvement, estimated to be present in 10% to 20% of patients with PCNSL. Such ocular involvement often presents as uveitis or optic nerve infiltration on imaging.4 Histologic verification of PCNSL with biopsy is necessary prior to initiation of treatment. Many patients with PCNSL who are symptomatic at presentation have lesions of considerable size with associated edema and mass effect and are consequently treated with corticosteroids to relieve the associated symptoms. The corticosteroids can rapidly “melt away” lymphomatous tumors, making stereotactic biopsy and resection difficult. Suspicion of PCNSL from imaging is crucial in the workup of these central nervous system lesions so that clinicians can refrain from prescribing corticosteroids prior to biopsy. An imaging-based suggestion of a diagnosis of PCNSL may allow for a diagnostic biopsy to be completed prior to initiation of corticosteroid administration. Quick implementation of treatment regimens can improve prognosis and quality of life for these patients. Our case highlights the notion that the characteristic features of PCNSL may be changing. Imaging of PCNSL in immunocompetent patients most commonly reveals a solitary infiltrative mass in the cerebral hemispheres, basal ganglia, or periventricular white matter.1,3 Recently, there have been increasing numbers of immunocompetent individuals presenting with multifocal intracranial lesions that involve both the supratentorial and infratentorial regions,2 as in our patient. Given the increasing incidence and insidious nature of PCNSL, it is essential to recognize this disease clinically and with imaging. It is imperative for radiologists and clinicians to be aware of the characteristic imaging findings of PCNSL in immunocompetent patients as well as the apparently evolving imaging findings of these lesions.
Published Online: March 26, 2015. doi:10.1001/jamaoncol.2015.0298. Conflict of Interest Disclosures: None reported. REFERENCES 1. Küker W, Nägele T, Korfel A, et al. Primary central nervous system lymphomas (PCNSL): MRI features at presentation in 100 patients. J Neurooncol. 2005;72(2):169-177.
2. Lanfermann H, Heindel W, Schaper J, et al. CT and MR imaging in primary cerebral non-Hodgkin’s lymphoma. Acta Radiol. 1997;38(2):259-267. 3. Partovi S, Karimi S, Lyo JK, Esmaeili A, Tan J, Deangelis LM. Multimodality imaging of primary CNS lymphoma in immunocompetent patients. Br J Radiol. 2014;87(1036):20130684. 4. Batchelor T, Loeffler JS. Primary CNS lymphoma. J Clin Oncol. 2006;24(8):1281-1288.
JAMA Oncology May 2015 Volume 1, Number 2 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://oncology.jamanetwork.com/ by a New York University User on 05/27/2015
jamaoncology.com
JAMA Oncology Clinical Challenge
Atypical Imaging Findings in an Immunocompetent Patient Julia Savage, MD; Douglas Quint, MD
A
B
Figure. Magnetic resonance images (MRIs) of the head obtained 8 months after patient’s first clinical visit. A, Axial T2-weighted MRI of the head at the level of the lateral ventricles demonstrates extensive ill-defined areas of increasing signal with only minimal associated mass effect involving the frontal lobe white matter, greater on the left than on the right. B, Contrast-enhanced T1-weighted MRI at the same level demonstrates abnormal patchy enhancement of the head of the left caudate nucleus and the deep anterior left frontal lobe white matter.
A previously healthy woman in her 50s presented with complaints of increasing forgetfulness, fatigue, and depressed mood after dealing with the deaths of several close relatives. She was diagnosed with depression and began treatment with antidepressant medication. After 8 months, she had worsening complaints. At that time, a family member reported that her memory problems had progressed. She was no longer able to find misplaced objects, remember appointments, or handle financial affairs. She was often subdued, her mood depressed, and her sleeping time increased. Clinical examination at that time revealed a flattened affect and a 22 of 30 Mini-Mental State Examination score. Findings were otherwise normal, and there were no focal neurologic deficits. Basic laboratory workup results were unremarkable. She was referred to a neurologist, who ordered contrast-enhanced magnetic resonance imaging (MRI) of the brain. The MRI (Figure) revealed extensive ill-defined areas of FLAIR (fluid-attenuated inversion recovery) and T2 signal abnormalities with additional enhancing nodular foci located within deep white matter structures, the basal ganglia, the caudate, the pons, and the midbrain. Also identified was enhancement of the interpeduncular cistern and cerebral peduncles, suggestive of leptomeningeal involvement.
jamaoncology.com
WHAT IS YOUR DIAGNOSIS?
A. Inflammatory demyelinating processes such as multiple sclerosis B. Neoplasms such as multicentric glioma, glioblastoma multiforme, and metastases C. Infectious causes including tuberculosis, neurosyphilis, and toxoplasmosis D. Primary central nervous system lymphoma
(Reprinted) JAMA Oncology May 2015 Volume 1, Number 2
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://oncology.jamanetwork.com/ by a New York University User on 05/27/2015
247
Clinical Review & Education JAMA Oncology Clinical Challenge
Diagnosis D. Primary central nervous system lymphoma
Discussion Following imaging, the patient underwent stereotactic brain biopsy, which revealed diffuse large B-cell lymphoma. Further workup revealed no other sites of disease, and Primary central nervous system lymphoma (PCNSL) was diagnosed. Contrast-enhanced MRI is the preferred imaging technique for evaluating PCNSL because it is useful for staging and biopsy planning (ability to identify spinal and/or leptomeningeal involvement). Histologically, PCNSL demonstrates dense cellular lesions that have the classic appearance of isodense to hyperdense areas on computed tomography scans and isointense to hypointense regions on T1-weighted MRI scans, which are hyperintense to white matter on T2-weighted MRI images. Unlike metastatic lesions, which often have a distinct border with contiguous brain parenchyma, PCNSL often demonstrates an infiltrative pattern within brain parenchyma. These lesions typically exhibit intense, homogeneous enhancement after contrast administration. In a study that looked at MRI features in 100 patients with PCNSL,1 only 1 patient had lesions that did not have strong or moderately strong contrast enhancement. Ring enhancement of the lesions can be seen in cases of PCNSL in immunocompromised individuals, such as those with human immunodeficiency virus (HIV), but such enhancement is considered a rare finding in immunocompetent patients.2 In the same study,1 90 of a subpopulation of 96 patients with PCNSL had significant edema on MRI imaging. Along with contrast enhancement, surrounding edema is another classic finding with PCNSL, which often results in local mass effect. In immunocompetent patients, PCNSL most frequently presents as a single lesion. In some cases, however, it can present as multiple lesions, which is a typical imaging finding in patients with HIV lymphoma. In the review of 100 patients with PCNSL,1 it was found that 65% of patients presented with only 1 lesion. Most frequently involving the cerebral hemispheres, PCNSL can also involve all areas of the craniospinal axis, including brain parenchyma, leptomeninges, spinal cord, and eyes. Within the ARTICLE INFORMATION Author Affiliations: Department of Radiology, University of Michigan Health System, Ann Arbor. Corresponding Author: Julia Savage, MD, Department of Radiology, University of Michigan Health System, 1500 E Medical Center Dr, UH B1G503, Ann Arbor, MI 48109-5030 ([email protected]).
248
brain itself, PCNSL can involve the cortex, deep structures such as basal ganglia, corpus callosum, and periventricular regions.3 Of 100 patients with PCNSL,1 cerebral hemispheric involvement was present in 38% (most commonly in the frontal lobes). The basal ganglia were involved in 16% of cases, corpus callosum in 14%, and periventricular regions in 14%. Leptomeningeal and cerebellar involvement was found to be the least likely location.1 Primary central nervous system lymphoma can also present with ocular involvement, estimated to be present in 10% to 20% of patients with PCNSL. Such ocular involvement often presents as uveitis or optic nerve infiltration on imaging.4 Histologic verification of PCNSL with biopsy is necessary prior to initiation of treatment. Many patients with PCNSL who are symptomatic at presentation have lesions of considerable size with associated edema and mass effect and are consequently treated with corticosteroids to relieve the associated symptoms. The corticosteroids can rapidly “melt away” lymphomatous tumors, making stereotactic biopsy and resection difficult. Suspicion of PCNSL from imaging is crucial in the workup of these central nervous system lesions so that clinicians can refrain from prescribing corticosteroids prior to biopsy. An imaging-based suggestion of a diagnosis of PCNSL may allow for a diagnostic biopsy to be completed prior to initiation of corticosteroid administration. Quick implementation of treatment regimens can improve prognosis and quality of life for these patients. Our case highlights the notion that the characteristic features of PCNSL may be changing. Imaging of PCNSL in immunocompetent patients most commonly reveals a solitary infiltrative mass in the cerebral hemispheres, basal ganglia, or periventricular white matter.1,3 Recently, there have been increasing numbers of immunocompetent individuals presenting with multifocal intracranial lesions that involve both the supratentorial and infratentorial regions,2 as in our patient. Given the increasing incidence and insidious nature of PCNSL, it is essential to recognize this disease clinically and with imaging. It is imperative for radiologists and clinicians to be aware of the characteristic imaging findings of PCNSL in immunocompetent patients as well as the apparently evolving imaging findings of these lesions.
Published Online: March 26, 2015. doi:10.1001/jamaoncol.2015.0298. Conflict of Interest Disclosures: None reported. REFERENCES 1. Küker W, Nägele T, Korfel A, et al. Primary central nervous system lymphomas (PCNSL): MRI features at presentation in 100 patients. J Neurooncol. 2005;72(2):169-177.
2. Lanfermann H, Heindel W, Schaper J, et al. CT and MR imaging in primary cerebral non-Hodgkin’s lymphoma. Acta Radiol. 1997;38(2):259-267. 3. Partovi S, Karimi S, Lyo JK, Esmaeili A, Tan J, Deangelis LM. Multimodality imaging of primary CNS lymphoma in immunocompetent patients. Br J Radiol. 2014;87(1036):20130684. 4. Batchelor T, Loeffler JS. Primary CNS lymphoma. J Clin Oncol. 2006;24(8):1281-1288.
JAMA Oncology May 2015 Volume 1, Number 2 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://oncology.jamanetwork.com/ by a New York University User on 05/27/2015
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