doi:10.1111/j.1750-3639.2009.00311.

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C O M M AY 2 0 0 9 C A S E 1

A 76-YEAR-OLD MAN WITH COGNITIVE AND NEUROLOGICAL

SYMPTOMS bpa_311 731..734

Hans Brunnström ; Michael Dictor1; Christer Nilsson2; Dag Gülich2; Elisabet Englund1
1

1
Department of Pathology
2
Department of Geriatric Psychiatry

than growing in sheets. The cells were small with a lymphoid

CLINICAL HISTORY appearance and round, oval or irregular nuclei, inconspicuous
A 76-year-old man presented with progressively worsening nucleoli, and scant cytoplasm (Figure 3a, 3b). Scattered mitoses, as
vertigo, memory and concentration impairment, spatial disorienta- well as necrotic areas and oedema, were present, and cells infil-
tion and mild expressive dysphasia for 6 months. His medical trated the meninges, perivascular spaces and vessel walls. The
history included hypertension and a surgically treated abdominal infiltrates extended from the left into the right frontal lobe, but were
aortic aneurysm. A few weeks before admission, headache, fatigue, absent in the temporal and parietal lobes. The affected brain tissue
weakness of the lower limbs and left arm, a tendency to fall to exhibited some reactive gliosis, mainly in the white matter, but no
the left, incontinence, and episodes of confusion occurred. Upon granulomas or plasmacytoid cells were detected. The histology was
admission the patient showed marked fatigue, confusion and neither typical of a central nervous system (CNS) lymphoma nor of
apathy, and a contrast-enhancing round lesion, 1 cm in diameter, an inflammatory disease.
was seen in the left temporal lobe on magnetic resonance imaging Immunohistochemically, the vast majority of the infiltrating
(MRI). Repeated cognitive testing demonstrated fluctuating defi- cells stained positive for CD3 (Figure 3c) and over half of them
cits in language, working and episodic memory, visuospatial were positive for CD2 and T-cell intracellular antigen 1 (TIA1).
ability, attention and psychomotor speed. A second MRI, Almost half of the cells were positive for the activated T-cell marker
performed one month after the first, showed attenuation of the granzyme B, and some for CD7. Occasional lymphocytes
previous lesion, with general signal enhancement in the leptom- expressed CD4, CD5, CD8 and CD30, while staining for the B-cell
eninges, a heterogeneous contrast-enhancing lesion measuring marker CD20 and for CD56, activin receptor-like kinase 1 (Alk1)
1 ¥ 2 cm in the left frontal lobe, and a smaller lesion near the left and T-cell receptor alpha/beta (TCR alpha/beta) was consistently
sylvian fissure (Figure 1). negative.
There was no sign of infection, and blood tests were normal.
Repeated lumbar punctures were performed; cerebrospinal fluid
(CSF) analyses showed slightly elevated counts of mononuclear
cells (7–10 ¥ 106 cells/L) that were cytologically normal. There
was evidence of severe blood brain barrier disruption with elevated
albumin levels and oligoclonal IgG bands on electrophoresis. The
levels of neurodegenerative markers were increased with a total tau
of 910 ng/L (ref < 400) and neurofilament protein of 2540 ng/L
(ref < 750). Extensive screening for infectious agents was negative.
Octreotide scintigraphy (octreotide used as a radiolabelled soma-
tostatin analogue for detection of neuroendocrine tumors, granulo-
matous disease, et cetera) showed uptake in the frontal and tempo-
ral lobe lesions (Figure 2a), a finding which led to the diagnostic
suggestion of neurosarcoidosis and to subsequent medication with
high dose corticosteroids. Initially, the treatment appeared to have a
beneficial effect, but the condition soon deteriorated clinically and
radiologically. Four months after the start of treatment the patient
died from aspiration pneumonia following a seizure episode.

PATHOLOGY
Macroscopically, a tumor-like mass, 5 ¥ 4 ¥ 3 cm in size with
poorly defined margins, was found in the centre of the left frontal
lobe within the white matter (Figure 2b; Luxol fast blue stain). No
other lesions were seen in the brain or the meninges.
Microscopic examination revealed a diffuse mononuclear cell
infiltrate with variable cell density infiltrating the neuropil rather Figure 1.

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© 2009 The Authors; Journal Compilation © 2009 International Society of Neuropathology
Correspondence

Figure 2.

732 Brain Pathology 19 (2009) 731–734

© 2009 The Authors; Journal Compilation © 2009 International Society of Neuropathology
 Correspondence

A B

Figure 3.

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Correspondence
DIAGNOSIS
Cerebral T-cell lymphoma.
DISCUSSION
Primary CNS lymphomas constitute about 6% of all primary brain
tumors and most are of B-cell phenotype. In Western countries only
2–5% of CNS lymphomas are derived from T-cells (3). Primary
CNS lymphomas of T-cell type (T-PCNSL) may appear at any age,
with a median age of about 60 years at diagnosis (10). Most
affected patients are immunocompetent, but T-PCNSL has been
reported in patients with human immunodeficiency virus (HIV)
or human T-lymphotropic virus 1 (HTLV-1) infections (9, 10).
Epstein-Barr virus (EBV) has not been linked to T-PCNSL (5, 8).
In the present case, a serologic test for HIV was negative, but
HTLV-1 status was not determined. In situ hybridization for EBV
on autopsy material was negative.
Patients with T-PCNSL are usually treated with chemotherapy
followed by irradiation, with or without initial corticosteroid treat-
ment. The prognosis is poor, with a 5-year disease-specific survival
of 17% and a median progression-free survival of 22 months(10).
Several factors have been linked to a worse prognosis, such as
advanced age, tumor in deep brain structures (cerebellum, brain-
stem, corpus callosum, and basal ganglia), elevated serum lactate
dehydrogenase, and elevated CSF protein levels (1, 6). In the
present case, the approximate duration of the illness was 14–15
months.
It may prove difficult to clinically diagnose a T-cell lymphoma of
the CNS. As in this case, MRI often shows a non-specific solitary
mass located in one of the cerebral hemispheres (7, 8, 10), and
brain biopsy is required for diagnosis. However, in the CNS, T-cell
lymphomas often present as infiltrating cells with small nuclei and
bland morphology, although pleomorphic or large cell phenotypes
are not infrequent (10), which explains why T-PCNSL may be
mistaken for non-neoplastic lymphoid infiltrates. In addition, pre-
viously administered corticosteroid treatment may further compli-
cate the histopatholoigcal diagnosis.
Genotypic analysis for TCR gamma (5) and other (4) TCR gene
rearrangements, in order to detect monoclonality, may be neces-
sary to establish the diagnosis, as no immunohistochemical marker
to detect T-cell monoclonality exists. In the present case, in which a
tumor diagnosis was not anticipated, the whole brain was routinely
fixed for several days in formaldehyde solution before sectioning
and staining, and genotypic analysis was therefore not possible.
However, the autopsy could provide a more solid base for diagnosis
than a brain biopsy would have done in this case, especially in the
light of the rather loosely scattered tumor cells and their non-
neoplastic appearance. The immunophenotype of T-PCNSL varies.
Staining may be positive for either or both CD4 and CD8 or as in
the present case both may be negative (2, 5, 8). Also, lymphoma
cells may lose their expression of CD5 and CD7 (5), as seen in
many cells in the present case. Although alternative conditions
(such as infection, granulomatous diseases and other inflamma-
tion) may be considered, the presentation of unusually fluctuating
734
© 2009 The Authors; Journal Compilation © 2009 International Society of Neuropathology
symptoms in a patient with progressive deterioration and contrast-
enhancing lesions on MRI should be considered to represent a
brain tumor until proven otherwise.
REFERENCES
1. Blay JY, Conroy T, Chevreau C, Thyss A, Quesnel N, Eghbali H,
Bouabdallah R, Coiffier B, Wagner JP, Le Mevel A, Dramais-Marcel
D, Baumelou E, Chauvin F, Biron P (1998) High-dose methotrexate
for the treatment of primary cerebral lymphomas: analysis of survival
and late neurologic toxicity in a retrospective series. J Clin Oncol
16:864–871.
2. Choi JS, Nam DH, Ko YH, Seo JW, Choi YL, Suh YL, Ree HJ (2003)
Primary central nervous system lymphoma in Korea: comparison of
B- and T-cell lymphomas. Am J Surg Pathol 27:919–928.
3. Deckert M, Paulus W (2007) Malignant lymphomas In: WHO
Classification of Tumors of the Central Nervous System Louis DN,
Ohgaki H, Wiestler OD, Cavenee WK (eds), pp. 188–192. IARC
Press: Lyon.
4. Dictor M, Warenholt J, Isinger A (2005) Resolving T-cell receptor
clonality in two and genotype in four multiplex polymerase chain
reactions. Haematologica 90:1524–1532.
5. Dulai MS, Park CY, Howell WD, Smyth LT, Desai M, Carter DM,
Vogel H (2008) CNS T-cell lymphoma: an under-recognized entity?
Acta Neuropathol 115:345–356.
6. Ferreri AJ, Blay JY, Reni M, ET AL (2003) Prognostic scoring system
for primary CNS lymphomas: the International Extranodal
Lymphoma Study Group experience. J Clin Oncol 21:266–272.
7. Kim EY, Kim SS (2005) Magnetic resonance findings of primary
central nervous system T-cell lymphoma in immunocompetent
patients. Acta Radiol 46:187–192.
8. Liu D, Schelper RL, Carter DA, Poiesz BJ, Shrimpton AE, Frankel
BM, Hutchison RE (2003) Primary central nervous system
cytotoxic/suppressor T-cell lymphoma: report of a unique case and
review of the literature. Am J Surg Pathol 27:682–688.
9. Marshall AG, Pawson R, Thom M, Schulz TF, Scaravilli F, Rudge P
(1999) HTLV-I associated primary CNS T-cell lymphoma. J Neurol
Sci 158:226–231.
10. Shenkier TN, Blay JY, O’Neill BP, ET AL (2005) Primary CNS
lymphoma of T-cell origin: a descriptive analysis from the
international primary CNS lymphoma collaborative group. J Clin
Oncol 23:2233–2239.
ABSTRACT
A 76-year-old man presented with cognitive symptoms, followed
by headache and weakness of the lower limbs and left arm. The
clinical course was progressive but fluctuating. On magnetic reso-
nance imaging (MRI), a contrast-enhancing lesion 1 cm in diam-
eter was seen in the left temporal lobe. This lesion became attenu-
ated and a new contrast-enhancing lesion 1 x 2 cm was seen in the
left frontal lobe on a subsequent MRI. Following additional tests,
treatment with corticosteroids for presumptive neurosarcoidosis
was started, however, he soon expired. At autopsy, there was a
tumor-like mass in the left frontal lobe. Pathologic evaluation
revealed a primary T-cell lymphoma of the central nervous system
(CNS). CNS T-cell lymphomas may be difficult to diagnose, even
histologically, due to their frequent small cell morphology and lack
of significant atypia.
Brain Pathology 19 (2009) 731–734