Diagnostic cytology
Fig. 16.6 Multinucleated giant cell in cerebrospinal fluid obtained from
an intraventricular shunt (Papanicolaou x MP).
reaction with a granulomatous process of infectious etiology or
a neoplasm. In addition to this type of foreign body reaction,
the presence of an intraventricular shunt is one of the causes of
eosinophilia in CSF.28,29
Key features of intraventricular shunt sample
• Highly cellular sample;
• Reactive ependymal cells;
• Epithelioid cells; and
• Multinucleated giant cells.
Various neoplastic processes, including leukemia, lymphoma,
carcinoma, melanoma, and primary CNS tumor, can be detected
by examination of CSF when they involve the ventricles or SAS.
Because the majority of patients with meningeal tumor have a
known tumor diagnosis at the time of subarachnoid dissemina-
tion, the question is usually whether cells similar to those in
the original biopsy sample are present in the CSF. In the few
cases in which patients without a previous diagnosis of neo-
plasia present with neoplastic cells in their CSF, knowledge of
the age of the patients, locations of other tumor masses in the
body, and morphology of the cells, including their expression of
specific antigens using immunohistochemistry, usually allow an
accurate diagnosis.
Because the most common pattern of leukemic involvement of
the CNS is infiltration of the SAS with little or no parenchy-
mal disease, examination of CSF is the most practical means of
establishing this diagnosis. This process is particularly common
in childhood leukemia, with acute lymphocytic leukemia (ALL)
and undifferentiated stem cell leukemia being among the most
prevalent types. With the advent in the 1960s of chemothera-
peutic protocols capable of producing systemic remission, CNS
relapse occurred in more than 50% of patients with ALL. This
observation led to routine administration of CNS prophylaxis
with radiation or chemotherapy, a practice that has dramatically
reduced the incidence of CNS disease.30-33 Nevertheless, this
Fig. 16.7 Immature myeloid cells in cerebrospinal fluid
(Papanicolaou x HP).
complication still occurs in 5-15% of cases, making periodic
examination of the CSF in patients with ALL a component of
standard protocols.34-36
The cells of ALL are typical blast forms with high nucleocy-
toplasmic ratios and round or convoluted nuclei. All varieties
of ALL, including null, B, T, and pre-B-cell types, can involve
the CSF, with a possible tendency for T-cell disorders to behave
in this fashion most frequently. When large numbers of blast
forms are present, they can be readily identified on routine prep-
arations, making immunohistochemical procedures for lym-
phoid antigens unnecessary. A problem in differential diagnosis
occasionally arises between recurrent leukemia and pleocytosis
due to infection in a patient with ALL. In this case, immunohis-
tochemical demonstration of polyclonality or of a monoclonal
population, expressing the same phenotype as in the marrow,
may resolve the problem.
Key features of acute lymphocytic leukemia
• Blast forms;
• High N/C ratio; and
• Round or convoluted nuclei.
Diagnostic difficulties may also arise when only a few abnor-
mal cells are encountered in a mixed cellular population in CSF
from a patient with ALL. Although some observers have used
antibodies against common acute lymphoblastic leukemia
antigen (CALLA) or expression of terminal deoxynucleotidyl
transferase in this setting to identify small populations of blast
forms, recurrent ALL should probably not be diagnosed using
this criterion alone because rare CALLA-positive cells can be
seen in individuals without leukemia.34,37 Another problem is
encountered when abnormal cells are seen in a specimen of low
cellularity. Even if a few blast forms can be identified with cer-
tainty, patients thus affected present a difficult clinical problem
in that evidence about whether they should be treated for CNS
relapse is conflicting. Although earlier studies suggested that the
presence of only rare blast forms in CSF samples of normal cell
counts should result in aggressive intrathecal therapy, further
studies in which such patients have been treated conservatively
have shown spontaneous clearing of the abnormal cells in some
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