Diagnostic cytology
Fig. 16.9 Adenocarcinoma metastatic to cerebrospinal fluid from the
breast (Papanicolaou x HP).
multiple foci impinge on the surface of the brain, cord, and
ventricles and shed diagnostic cells into CSF.46,47 The cells may
be few and are frequently mixed with a dense infiltrate of lym-
phocytes and macrophages, making multiple samplings and
careful study of the fluid necessary to establish the diagnosis.
The application of anticytokeratin or anticarcinoma antibodies
can be extremely useful in these situations to highlight rare
malignant cells within an inflammatory background.
In approximately 5% of cases of brain metastases, a pat-
tern consisting almost entirely of subarachnoid involvement is
encountered. This condition, termed meningeal carcinomatosis
or carcinomatous meningitis, may be difficult to diagnose clini-
cally, particularly in patients without previous documentation
of cancer. The demonstration of cranial nerve palsies or com-
pression of spinal nerve roots may lead to suspicion of this proc-
ess, and examination of CSF is the most practical and definitive
means of establishing this diagnosis.
Carcinomas of the lung and the breast, with their tendency to
disseminate hematogenously, are the tumor types encountered
most frequently in CSF, as a result of both multifocal metastases
and meningeal carcinomatosis.2,48-52 Although adenocarcinoma
of the stomach is considerably less common than it was in the
early part of this century, cases of meningeal carcinomatosis from
this source are still encountered, and this tumor type remains
responsible for many cases of meningeal carcinomatosis that
appear with an occult primary.49 Other tumor types reason-
ably frequent in the population, including renal cell carcinoma,
adenocarcinoma of the colon, and transitional cell carcinoma of
the bladder, are uncommonly seen in CSF because they tend to
produce solitary brain metastases rather than multifocal lesions
or meningeal carcinomatosis. In addition to these tumor types
that involve the SAS hematogenously, some neoplasms arising in
the head and sinuses, such as squamous cell carcinoma in adults
and embryonal rhabdomyosarcoma in children, enter the CSF
by direct invasion of bone or travel along cranial nerves. Rarely,
a similar process occurs in the pelvis when squamous cell carci-
noma of the uterine cervix or adenocarcinoma of the colon grows
directly into the subarachnoid space of the spinal cord.2,53
The morphology of these cells is generally the same as their
presentation in other types of cytologic specimens (Fig. 16.9)
except, however, for a greater tendency for carcinoma cells to
shed singly or in loose clusters rather than in cohesive tissue
fragments. This characteristic is particularly obvious with breast
carcinoma, which usually occurs in CSF as single cells and only
rarely forms balls or a morula.
Cutaneous melanoma is among the tumor types with the
greatest likelihood of CNS metastasis. In the majority of fatal
cases of disseminated melanoma, nervous system involvement
was found at the time of autopsy.54 Cells can be identified in CSF
from patients with multifocal lesions of the brain and cord if the
SAS space is invaded, and tumor spread is readily diagnosed in
cases of diffuse subarachnoid melanomatosis. In a patient who
presents with melanoma in the CSF in the absence of an identi-
fied primary tumor in the skin or mucous membranes, it may be
impossible to determine whether the process actually began in
the meninges as a primary meningeal melanoma.55
Cells of malignant melanoma are characteristically large and
have coarse nuclear chromatin and prominent macronucleoli
(Fig. 16.10). When cytoplasmic melanin pigment is present,
Fig. 16.10 Cells of malignant melanoma in cerebrospinal fluid ((A) Papanicolaou x HP; (B) Diff-Quick x HP).
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