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Infiltration of the Central Nervous System as a
Presentation Form of Early Stage Chronic
Lymphocyte Leukemia
To the Editor: Symptomatic infiltration of the central nervous system by
chronic lymphocytic leukemia (CLL) is extremely rare [1] and is accom-
panied by cerebro-spinal fluid (CSF) lymphocytosis. In autopsy series [2],
however, infiltration of the brain or spinal cord is common in CLL, par-
ticularly in later stages, but patients are asymptomatic. We present a case
of CLL (Rai stage 0), which began with neurological manifestations, sec-
ondary to leukemic meningeal infiltration.
A 65-year-old man with a history of chronic liver disease due to hepatitis
C virus was admitted with progressive headache, weight loss, and night
sweats, recently accompanied by confusion, diplopia, and dysphagia.
Physical examination revealed no peripheral lymphadenopathies or vis-
ceromegalies. The WBC count was 25 × 10
9
/l (59% lymphocytes, 33%
neutrophils). Peripheral smear lymphocytes were predominantly mature
with 15% prolymphocyte forms. Hemoglobin was 13.4 g/dl and platelets
205 × 10
9
/l. Chest and abdominal CT scans were normal, as were cranial
MRI and CT scans. A lumbar puncture gave a WBC count of 586/mm
3
(85% lymphocytes morphologically similar to those in the peripheral
blood). Extensive microbiological studies were negative. A bone marrow
smear and biopsy showed a diffuse infiltration of mature lymphocytes and
20% prolymphocyte forms. Phenotyping of the lymphoid population of the
CSF and peripheral blood showed a monoclonal lambda light chain ex-
pression, a positive result for CD
19
, FMC7, CD
23
, and coexpression of
CD
19
and CD
5
, in 87% of the cells. B cell CLL Rai stage 0, with meningeal
infiltration, was diagnosed. Polychemotherapy was initiated according to
the COP scheme, with intrathecal methotrexate being added on days 1 and
10 of each cycle. After the first cycle the patient showed a clear improve-
ment in neurological signs and the CSF WBC count fell to 60/mm
3
. He
died after the second cycle of chemotherapy due to bilateral pneumonia. No
autopsy was performed.
The finding of neurological symptoms as the initial manifestation of the
disease is exceptional, and only a few cases have been reported (Table I).
In our case, although the diagnosis of B cell CLL was suspected from the
morphological and cytochemical findings in the peripheral blood and bone
marrow, the monoclonal character of the lymphocyte proliferation needed
to be shown to provide confirmation. This monoclonality was demon-
strated by the presence of a single lambda light chain on the cell surface of
B lymphocytes by flow cytometry [3]. The positive result of CD
23
in the
absence of lymphadenopathies or splenomegaly ruled out the possibility of
a mantle lymphoma, which should always be considered in the differential
diagnosis [4]. The positive result for FMC7 was interpreted as the expres-
sion of a possible evolutionary stage towards a prolymphocytic leukemia.
Finally, the importance of immunophenotyping CSF lymphocytes to reach
a diagnosis of CNS infiltration by CLL should be noted. When faced with
a neurological picture with peripheral lymphocytosis, even in the absence
of peripheral lymphadenopathies and visceromegalies, CLL should be in-
cluded in the differential diagnosis, as, although its incidence is low, meth-
ods are available to confirm the tumoral origin of the proliferation, as well
as to provide specific therapy.
I. PE ´ REZ FERNA ´ NDEZ
Hematology Service, ‘‘Virgen de la Victoria’’
University Hospital, Ma ´ laga, Spain
F. SALGADO ORDO ´ N ˜ EZ
Internal Medicine Service, ‘‘Virgen de la Victoria’’
University Hospital, Ma ´ laga, Spain
TABLE I. Symptomatic Infiltration of CNS: A Presentation Form of CLL*
Reference Sex/age Stage
a
CNS
localization
Neurological
findings
Korsager et al. [5] F/64 II CSF Dementia
Cash et al. [6] M/59 0 CSF Blindness
M/47 0 CSF Headache/gait disturbance
Fain et al. [7] F/57 II Pituitary CSF Bitemporal hemianopsia; panhypopituitarism
Cramer et al. [2] F/87 0 Subarachnoid Agitated
Current report M/65 0 CSF Headache; confusion
*CNS, central nervous system; CLL, chronic lymphocytic leukemia; CSF, cerebro-spinal fluid.
a
At diagnosis of CNS involvement.
American Journal of Hematology 58:339–342 (1998)
© 1998 Wiley-Liss, Inc.