PART TWO
Diagnostic cytology
herpes simplex, herpes zoster, JC virus, and SV40-PML virus of
progressive multifocal leukoencephalopathy (PML). Although
cells containing the characteristic nuclear inclusions of these
viruses can be demonstrated in open biopsy and needle biopsy
specimens of the parenchymal lesions, inclusion-bearing cells
are only rarely identified in CSF. To date, the literature contains
only two reported cases of herpes encephalitis and one case of
CMV infection in a patient with acquired immunodeficiency
syndrome (AIDS) in whom cells with typical inclusions were
seen in CSF.2,8-11 The use of polymerase chain reaction (PCR)
techniques to amplify the genome of herpes simplex virus (HSV)
from CSF has become the diagnostic procedure of choice.12,13
CSF PCR is a reliable means for diagnosis of CMV infection in
patients with AIDS.14,15
Key features of viral meningoencephalitis
• Predominant lymphocyte response; and
• Reactive lymphocytes.
A nonspecific lymphocytosis may be seen as a result of
CNS infections of other etiologies. Wilber and colleagues have
described an atypical lymphocytic proliferation with plasmacy-
tosis in the CSF of patients with cerebral cysticercosis.16 Simi-
lar findings have also been reported in the CSF of patients with
Lyme disease.17
Three types of CNS disorders are encountered in patients
with AIDS. First is AIDS encephalopathy resulting directly or
indirectly from infection of cells within the brain or spinal cord
by the AIDS virus. Histologically, the lesions consist of glial nod-
ules, chronic inflammation, gliosis, and sometimes multinucle-
ated giant cells. The CSF from these patients usually contains
only a nonspecific chronic inflammatory infiltrate, although
rarely, multinucleated giant cells may be encountered. The sec-
ond group of abnormalities consists of opportunistic infections,
which are most frequently produced by
Cryptococcus neoformans,
Toxoplasma gondii,
mycobacteria,
Candida,
and viruses such as
CMV and PML. Although these organisms or their characteris-
tic cellular inclusions can frequently be demonstrated by open
brain biopsy specimens or needle aspirates of the cerebral
lesions, their manifestations in CSF are usually nonspecific,
with the exception of rare cases of CMV inclusion-bearing cells
in CSF.11
Among these infections, cryptococcal meningitis is the
only process in which examination of CSF yields a specific diag-
nosis in a high percentage of cases. The third disorder involv-
ing the CNS of patients with AIDS is neoplasia, which is most
frequently lymphoma. Examination of the CSF often reveals
the characteristic malignant cells of lymphoma both in AIDS
patients with primary CNS lymphoma involving the subarach-
noid space and in patients with systemic lymphoma and CNS
metastases. Because the majority of these lymphomas are of the
B-cell type, immunohistochemical markers are often helpful in
establishing the diagnosis.
Key features of AIDS encephalopathy
• Non-specific chronic inflammatory infiltrate; and
• Rare occurrence of multinucleated giant cells.
Cryptococcus neoformans
is the most frequent cause of fun-
gal meningitis. This organism usually enters the body through
the respiratory system and disseminates to the CNS hematog-
enously.18 Cryptococcal meningitis may be a complication of
immunosuppression, as in recipients of organ transplants, in
patients with lymphoma and leukemia, and in patients with
AIDS. This disease occasionally occurs, however, in otherwise
healthy individuals. In immunosuppressed patients, in particular,
there may be very little cellular reaction and the CSF may con-
tain multitudes of organisms. In some cases, however, a brisk
inflammatory reaction may occur. The cells can be mainly lym-
phocytes, although polymorphonuclear leukocytes or macro-
phages occasionally predominate. The organisms are frequently
demonstrable morphologically as round yeast forms of variable
diameters, which produce thin-necked buds (Fig. 16.4).19-21 The
organisms commonly have a refractile appearance, possibly
because of the mounting medium trapped between the capsule
of the organism and the coverslip (see Fig. 16.4). Organisms
with this presentation can be mistaken for particles of glove
powder, which are also refractile.
Cryptococci often possess a thick, mucopolysaccharide cap-
sule that stains readily with mucicarmine, Alcian blue, and col-
loidal iron stains. Organisms without a prominent capsule are
sometimes encountered, however, and these structures may
be difficult to distinguish from partially lysed erythrocytes or
even bubbles of air or water, which may be trapped under the
coverslip. The presence of true buds is useful in distinguishing
the organisms from these other structures.
Cryptococci must also be distinguished from other types of
budding yeasts, such as
Blastomyces dermatitidis
and
Histoplasma
capsulatum,
which occur only rarely in CSF. In addition to the
thin-necked buds and mucopolysaccharide capsule charac-
teristic of
Cryptococcus
, this organism usually displays a wide
range of diameters within an individual specimen.
Blastomyces
is uniformly large, with diameters of 8-12 pm, and
Histoplasma
is uniformly small, generally 1-5 pm in diameter. In addition
to diagnosing cryptococcal meningitis cytologically, the organ-
ism may be identified by its growth characteristics in culture
and by demonstration of cryptococcal antigen by radioimmu-
noassay.
Key features of fungal meningitis
• Brisk mixed inflammatory reaction; and
• Identification of organisms.
Fig. 16.4 Budding yeast of
Cryptococcus
in cerebrospinal fluid
(Papanicolaou x HP).
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