16
Central Nervous System
of them. The approach suggested by McIntosh and Ritchey for
patients with ALL is to treat them for CNS relapse if the CSF con-
tains more than 10 cells/pL with blast forms or with less than
10 cells/pL if blast forms predominate.38 For patients in whom
only rare blast forms are seen in CSF samples with less than
5 white blood cells/pL, however, their policy is only to repeat the
examination of CSF every few months to 1 year provided that
the patient is in systemic remission and lacks CNS symptoms.
Involvement of the CNS also occurs in patients with acute
myelogenous leukemia (Fig. 16.7), acute promyelocytic leuke-
mia, acute monocytic leukemia, and acute myelomonocytic
leukemia. Patients with acute myelomonocytic leukemia and
inversions of chromosome 16, in particular, are at risk for hav-
ing meningeal involvement at the time of presentation.39 The
absolute incidence of CSF leukemia is lower than in ALL owing
to the shorter survival times of these patients, but with increased
survival times of these patients, as new therapeutic protocols are
developed, the incidence of this complication can be expected
to increase. CNS leukemia may occur either at initial presenta-
tion or at relapse. The cells resemble the blast forms seen in the
marrow and peripheral blood and can be readily identified on
routine preparations. In contrast to the acute leukemias, CNS
involvement is unusual in the chronic phase of myelogenous
leukemia. When patients enter the accelerated phase or blast
crisis, however, immature myeloid forms may be observed in
the CSF of some patients.2
Symptomatic CNS involvement is so rare in patients with
chronic lymphocytic leukemia and prolymphocytic leukemia
that an infectious process should be considered first when they
develop signs of meningeal disease.40-42 Because of their immu-
nocompromised status, viral and cryptococcal meningitides are
common in this group of patients, and the lymphocytosis some-
times produced may be difficult to distinguish from leukemic
involvement.7 Application of immunohistochemical lymphoid
markers often resolves the problem. If these procedures are not
available, a careful search for cryptococcal infection and a con-
servative position of awaiting spontaneous resolution of a viral
infection are approaches that may establish the diagnosis.
Lymphoma
As with leukemia, the most common pattern of CNS involve-
ment from systemic lymphoma is subarachnoid dissemination
with little or no parenchymal disease. Occasionally, however,
multifocal infiltrates occur within the brain and spinal cord of
patients with bulky disease elsewhere. Although primary CNS
lymphoma generally presents as a solitary mass lesion, CSF dis-
semination is common during the course of this disease.
The varieties of lymphoma that tend to seed the SAS are
among the most aggressive histologic types and include large-
cell lymphoma (Fig. 16.8) and immunoblastic sarcoma in
adults as well as lymphoblastic lymphoma, Burkitt's lym-
phoma, and undifferentiated lymphoma in children. Detec-
tion of these cells is based on the presence of a monomorphous
population with cellular characteristics of the lymphoma type
demonstrated elsewhere in the patient. Because the majority of
lymphomas involving the CSF are the B-cell type, whereas reac-
tive lymphocytoses contain mainly T cells, the demonstration
of a monoclonal population expressing one type of light chain
and one type of heavy chain is a helpful diagnostic adjunct in
difficult cases.43,44 If the phenotype has previously been demon-
strated in nodal tissue, documentation of the same pattern in
cells in CSF allows a specific and definitive diagnosis. For T-cell
lymphoma, interpretation of lymphoid marker panels may be
more difficult owing to the mixture of neoplastic and reactive
T cells frequently encountered.45
The better differentiated forms of lymphoma, including nod-
ular lymphoma, and small-cell lymphoma of the cleaved and
noncleaved varieties, in contrast, uncommonly produce symp-
tomatic CNS involvement. As with chronic lymphocytic leuke-
mia, infectious processes should be considered in patients who
have these disorders and who develop neurologic problems. The
immunohistochemical application of lymphoid antibodies is
often definitive in distinguishing lymphoma from reactive con-
ditions in samples of CSF from these patients. Hodgkin's dis-
ease, also, rarely involves the CNS directly and is almost never
seen in the SAS or CSF.
Metastatic Carcinoma and Meningeal
Carcinomatosis
The ability to diagnose metastatic carcinoma to the CNS by
examination of CSF is directly proportional to the extent to
which the process involves the ventricular system and SAS. In
cases in which the metastatic lesions are confined to the brain
and spinal cord parenchyma or to the bones and extradural
space of the skull or spine, cells have no access to the CSF. In
many cases of brain metastases, however, large lesions or small
«
Fig. 16.8 Large-cell lymphoma in cerebrospinal fluid ((A) Papanicolaou x HP; (B) Diff-Quik x HP).
445
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