NEUROIMAGING HIGHLIGHTS

COPYRIGHT © THE AUTHOR(S), 2020. PUBLISHED BY CAMBRIDGE UNIVERSITY PRESS ON BEHALF OF THE CANADIAN JOURNAL OF
NEUROLOGICAL SCIENCES INC.

Neuroimages and Neuropathology of a
Stroke-Like Cerebral Lymphomatoid
Granulomatosis
Massimo Marano , Chiara Brunelli, Costanza De Marco, Maurizio Martini,
Carlo Cosimo Quattrocchi, Libero Lauriola, Vincenzo Di Lazzaro
Keywords: Brain neoplasm, Lymphoma, Vasculitis, Brain stereotactic biopsy, Glioma, stroke mimic

doi:10.1017/cjn.2020.133

A 70-year-old man presented to the Emergency Department
reporting the acute onset of non-fluent aphasia, hyposthenia,
and hemi-anesthesia of the right body. Brain computerized
tomography revealed a subcortical hypodense lesion in the
middle cerebral artery territory. Neck ultrasounds of internal
and external carotid arteries and of the vertebral arteries showed
a focal moderate stenosis of the left internal carotid artery due to
a soft atheromasic plaque. These findings that were initially
consistent with a diagnosis of an ischemic stroke were not
confirmed by magnetic resonance (MR). The latter showed an
hyperintense lesion on FLAIR and T2-weighted sequences
located in the left centrum semiovale, corona radiata, and
thalamus, with a well-defined regular rim and a mild compressive effect on the lateral ventricle, with diffusivity restriction but
without ADC reduction and with a punctate and serpiginous
gadolinium enhancement on T1 sequences (Figure 1). Within
the first day of observation, the patient started complaining
progressive mental deterioration, in absence of any other possible causes, and a total body CT scan excluded any other organ
involvement. Patient was then referred to the neurosurgeon in
order to perform a brain biopsy. The neuropathology was
compatible with the diagnosis of cerebral lymphomatoid granulomatosis (LG) (Figure 1).
Central nervous system (CNS) lymphoproliferative disorders
include the primary diffuse large B-cell lymphoma of the CNS
and a variety of other lymphomas and related lymphoproliferative
conditions, such as the LG. LG is a rare angiocentric and
angiodestructive lymphoreticular proliferative disorder.1 It is an
EBV-driven systemic disease, which usually involves lungs
followed by the skin and the brain. Isolated CNS LG (CLG) is
an extremely rare condition, and it is only anecdotally reported in
literature and poorly characterized on a neuroradiological and
clinical point of view. Its pathogenesis and biological behavior
are debated and, according to some authors, the isolated CLG is
not related to EBV and shows a better prognosis overall.1,2 Our
case is in line with such observation since the immunophenotype
– in situ hybridization analysis of EBV-encoded small RNAs
(EBER ISH) – of the pathological specimen was negative for the
EBV virus, whilst the immunoglobulin IgH gene (FR3/JH) and
the T-cell receptor (TcRγ) rearrangement showed a polyclonal
pattern as documented in LG cases with negative EBV.1 On the

114
https://doi.org/10.1017/cjn.2020.133 Published online by Cambridge University Press

Can J Neurol Sci. 2021; 48: 114–115

Figure 1: An undefined edematous lesion in the left thalamus/corona
radiata seen at the brain MRI axial FLAIR (A), axial DWI (B), and
coronal T2-weighted sequences as a hyperintense lesion (C) with a
serpiginous gadolinium enhancement featuring its core at axial (D),
sagittal (E), and coronal (E) T1-weighted images. The hematoxylin–
eosin stain showed a cerebral tissue with vascular structures surroundend by a polymorphous lymphoid infiltrate (G, 100×). In detail at higher
magnification (inset in G, 200×) the reticulin stain demonstrated the
presence of dispersed reticular fibers due to the angiodestructive behavior of the disease. Immunostaining showed few and isolated CD20
activated B cells (H, 400×) in an abundant CD3 lymphocyte background
(I, 100×).

From the Unit of Neurology, Neurophysiology, Neurobiology, Department of Medicine,
Università Campus Bio-Medico di Roma, via Álvaro del Portillo 21, 00128 Rome, Italy
(MM, VDL); Department of Anatomic Pathology and Histology, “A. Gemelli” University Polyclinic Foundation, Rome, Italy (CB, CDM, MMartini, LL); and Radiology Unit,
Università Campus Bio-Medico di Roma, via Álvaro del Portillo 21, 00128 Rome, Italy
(CCQ)
RECEIVED JANUARY 13, 2020. FINAL REVISIONS SUBMITTED MAY 18, 2020. DATE OF
ACCEPTANCE JUNE 25, 2020.
Correspondence to: Massimo Marano, Unit of Neurology, Neurophysiology, Neurobiology, Department of Medicine, Università Campus Bio-Medico di Roma, via Álvaro del
Portillo 21, 00128 Rome, Italy. Email: m.marano@unicampus.it

LE JOURNAL CANADIEN DES SCIENCES NEUROLOGIQUES

other side, the WHO LG grading relies on the amount of EBV
positive cells and the presence of a secondary CNS involvement
predicts a lower life expectancy.
Differentiating primary lymphoproliferative disorders from
other brain lesions could be difficult, and the histological
analysis results essential in the diagnosis. The presence of
an angiodestructive process makes it possible the differentiation with brain lymphomas which share with the CLG the
angioinvasive features.3 Pathognomonic neuroimages have not
been ever identified, but the most common MR finding is a
linear or a “multiple punctuate” enhancement along perivascular
spaces. Large mass-like lesions, ring-enhancement lesions, and
leptomeningeal involvement have also been reported.4,5 CLG
lacks any clinical or radiological specific sign. Vasculitis,
demyelinating, infectious, and neoplastic disorders could
present similar features making only histopathology diagnostic,
so far. The clinical presentation is highly variable, and the
available cases are described as subacute disorders leading to
a progressive neurological deterioration. Patients generally
present with headache, seizures, altered consciousness, motor
progressive deterioration and dementia, and cranial nerve
palsies have also been described. A stroke-like presentation is
very rare.1,2 This could be justified by the vascular and perivascular destructive process, which produced a microvascular
damage with consecutive ischemic changes of the surrounding
tissue, thus explaining the possibility of an acute stroke-like
clinical presentation.

Volume 48, No. 1 – January 2021
https://doi.org/10.1017/cjn.2020.133 Published online by Cambridge University Press

DISCLOSURES
The authors have no conflicts of interest to declare.
ETHICAL APPROVAL
The research has been given ethical approval and is conducted
in accordance with the declaration of Helsinki.
STATEMENT OF AUTHORSHIP
MM, CCQ, and VDL collected clinical and radiological data;
CB, CDM, MMartini, and LL provided brain pathology samples
and description.
REFERENCES
1. Lucantoni C, De Bonis P, Doglietto F, et al. Primary cerebral
lymphomatoid granulomatosis: report of four cases and literature
review. J Neurooncol. 2009;94:235–42.
2. Roschewski M, Wilson WH. Lymphomatoid granulomatosis.
Cancer J. 2012;18:469–74.
3. Sugita Y, Muta H, Ohshima K, et al. Primary central nervous system
lymphomas and related diseases: Pathological characteristics and
discussion of the differential diagnosis. Neuropathology
2016;36:313–24.
4. Patsalides AD, Atac G, Hedge U, et al. Lymphomatoid granulomatosis: abnormalities of the brain at MR imaging. Radiology
2005;237:265–73.
5. Tateishi U, Terae S, Ogata A, et al. MR imaging of the brain in
lymphomatoid granulomatosis. AJNR Am J Neuroradiol.
2001;22:1283–90.

115