Pleural, Peritoneal, and Pericardial Effusions
Key features of melanoma
• Effusion possibly straw-colored, or light to dark
• Cells isolated or in small to medium-sized clusters;
• Cytoplasm usually pigmented, light to heavy brown,
but may be amelanotic.
Mesotheliomas have attracted much international attention
since Wagner and co-workers in South Africa described an asso-
ciation between this neoplasm and the inhalation of asbestos.195
Apart from the epidemiologic and etiologic aspects of mesothe-
lioma that this publication introduced, it opened up anew the
question of whether the neoplasm, mesothelioma, really exists,
a controversial subject at that time.196
The controversy existed because diffuse malignant mesothe-
lioma of the epithelial type frequently shows morphologic fea-
tures similar to those of adenocarcinoma metastatic to a serous
membrane. It was therefore believed that unless an occult
adenocarcinoma could be excluded by complete necropsy, the
diagnosis of mesothelioma was never justified, and even when
adenocarcinoma was considered to be ruled out, the diagnosis
had to be viewed with a degree of skepticism. Any doubts about
the existence of mesothelioma have been dispelled by nearly
five decades of accumulated literature dealing with epidemio-
logic, etiologic, clinical, routine morphologic, histochemical,
electron microscopic, and immunocytochemical aspects of the
Primary neoplasms of the serous membranes classified as
mesotheliomas may be divided into two types: diffuse and local-
ized. The diffuse mesotheliomas are malignant; the localized
neoplasms are either benign or malignant, mostly the former.
In fact, some variants of localized mesotheliomas should, per-
haps, be designated as either fibromas or fibrosarcomas. From
the point of view of the cytology of serous effusions, it is only
the diffuse malignant mesotheliomas that contribute cells of
diagnostic significance, and even then, it is only the epithelial
variant that gives rise to a distinctive cytologic picture.
In this context, the term
does not include the
rare primary papillary serous neoplasm of the peritoneum that
occurs in women. This neoplasm, which may be disseminated
throughout the peritoneal cavity, is morphologically similar to
ovarian papillary serous neoplasms and is quite distinct from
mesothelioma. No account of the cytologic manifestation of
this condition in ascitic fluid appears to have been published.
Diffuse malignant mesothelioma may arise on the pleura,
peritoneum, pericardium, or tunica vaginalis of the testis. It most
commonly arises from the pleura or peritoneum, especially the
former; it rarely arises from the pericardium or tunica vagina-
lis testis. The neoplasm usually affects men in their sixth and
seventh decades of life and may develop multifocally in more
than one serous cavity. Even though it may appear to develop
in only one serous cavity, by the time a patient dies it frequently
involves more than one, probably due to spread by contiguity.
In the earliest stages of their disease, most patients with dif-
fuse malignant mesothelioma develop symptoms and signs of
effusion. A pleural effusion may be clinically silent, being dis-
covered only on a routine X-ray film of the chest; on the other
hand, patients may experience breathlessness or an aching
pain in the chest. A patient with peritoneal mesothelioma may
complain of abdominal swelling. Consequently, one of the first
specimens that the laboratory receives from a patient with dif-
fuse malignant mesothelioma is likely to be pleural or perito-
neal effusion.
Histologically, the diffuse form of diffuse malignant meso-
thelioma has either an epithelial or a sarcomatous appearance.
The epithelial variant is either a well-differentiated papillary
form (hence its similarity to metastatic adenocarcinoma) or a
medullary form, or a combination of these, whereas the sarco-
matous variant is composed of spindle cells, sometimes accom-
panied by a large amount of collagen. The epithelial type of
mesothelioma is the more common; however, the two types
frequently coexist.
As to the histogenesis of these two types of mesothelioma, it
is easy to imagine the monolayer of mesothelial cells undergo-
ing neoplastic transformation to produce mesothelioma of the
epithelial type. In histologic sections of mesotheliomas, it is not
uncommon to find segments of mesothelium that appear to
have undergone such a transformation to form neoplastic pap-
illary fronds. On the other hand, accumulating evidence now
suggests that the submesothelial mesenchyma retains the poten-
tial to differentiate into either epithelial or sarcomatous types of
neoplasm or both.202
As mentioned earlier, the first manifestation of diffuse malig-
nant mesothelioma is usually caused by pleural or peritoneal
effusion. As this stage, both layers of the serosa are studded with
innumerable tiny neoplastic nodules, which may be radiologi-
cally undetectable. As the disease progresses, the nodules increase
in size and coalesce to produce a thick rind of neoplasm on each
serosal surface. The two layers eventually fuse, and the amount
of space available for effusion thus is considerably diminished
or even completely obliterated. As the neoplasm continues to
grow, it causes bulging of either the hemithorax or the abdo-
men, with displacement or constriction of underlying organs.
Many accounts of the cytologic manifestations of diffuse malig-
nant mesothelioma in serous fluids have been given. They deal
almost exclusively with the cytology of diffuse malignant mes-
othelioma of the epithelial type, which is recognizable from
cells exfoliated into serous effusions. The cytologic diagnosis of
diffuse malignant mesothelioma of the epithelial type is a two-
step process. First, the cells in the fluid must be recognized as
being of mesothelial lineage, and second, they must be recog-
nized as neoplastic. The first step is usually not difficult because
mesothelioma cells of the epithelial type retain the morpho-
logic features of benign mesothelial cells with such fidelity
that they are recognized as being of a mesothelial nature.203 In
smears, the morphologic features of non-neoplastic mesothelial
cells, recapitulated in their neoplastic form, are those of shape;
cytoplasmic staining reaction; nuclear position, size, and shape;
nucleolar prominence; and types of intercellular articulation, as
well as the formation of small or large mosaic sheets of cells and
irregularly shaped clusters with knobby contours.
Malignant mesothelioma cells should show these morpho-
logic characteristics to be recognized as mesothelial, but they
should also be different enough from the normal or hyper-
trophic mesothelial cells to appear neoplastic. Usually it is not
difficult to perceive their mesothelial lineage, but it may be dif-
ficult to conclude that they are malignant because the standard
nuclear feature of malignancy may be poorly represented. Nev-
ertheless, our experience with cytologic preparations of pleural
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