chapter 4 The pleural, pericardial, and peritoneal cavities are lined by a single layer of flat mesothelial cells called the serosa. Normally, these cavities are collapsed and contain only a small amount of fluid, enough to lubricate the adjacent surfaces as they move over each other with respiration, heartbeats, and intestinal peristalsis. In disease states, a greater amount of fluid—an effusion—accumulates. Effusions are classified clinically as transudative or exudative. Transudates result from an imbalance of hydrostatic and oncotic pressures. Common causes are congestive heart failure (CHF), cirrhosis, and the nephrotic syndrome. Transudates have a low lactate dehydrogenase (LDH) and low total protein concentration. Exudates result from injury to the mesothelium, as occurs with malignancy, pneumonia, lupus, rheumatoid pleuritis, pulmonary infarction, or trauma. Exudates have relatively high LDH and total protein concentrations. The distinction is made by protein concentration measurements performed in the clinical laboratory. The distinction is important, because pleural involvement by a malignancy causes formation of an exudate, and therefore cytologic examination is not needed for a transudate.1 Malignant tumors are a common cause of exudate formation because the serosal surfaces are a frequent site of metastasis for many tumors, as well as the site of origin for the asbestos-related tumor malignant mesothelioma. Specimens are obtained by inserting a needle into the pleural space (thoracentesis), pericardial space (pericardiocentesis), and peritoneal cavity (paracentesis). Care should be taken when withdrawing large amounts of pleural fluid because of the rare but life-threatening complication of reexpansion pulmonary edema.1–3 By contrast, large volume paracentesis (e.g., 4 to 6 L) is relatively safe, and there are even reports of draining 20 L of ascitic fluid at one time.4 Although peritoneal fluid is usually obtained through the abdominal wall, in women it can also be aspirated from the cul-de-sac through the vagina (culdocentesis). Less commonly, fluid is obtained by suction during thoracic, abdominal, or cardiac surgery. Fluid is collected in clean containers and sent unfixed to the laboratory. To prevent clotting, which widely disperses cells, thus hindering their evaluation, fluid can be collected in heparinized bottles containing 3 units of heparin per milliliter of capacity.5 If heparinized bottles are not available, the heparin should be poured into the bottle before the fluid is collected; specimen contact with glass results in rapid clotting. Fluid is refrigerated at 4° C until the time of slide preparation. An effusion specimen is remarkably hardy—it can be refrigerated for 2 weeks or longer without compromising cellular morphology or antigenicity for immunostains.6 A variety of slide preparation methods are available. Slide preparation begins by shaking the container to evenly disperse the cells and then centrifuging a 50 mL aliquot (or the entire specimen if less than 50 mL). The supernatant is discarded and the sediment used to prepare smears, cytocentrifuge preparations,7 or thinlayer preparations.7,8 The slides are usually alcohol-fixed and Papanicolaou-stained. If a hematologic malignancy is suspected, air-dried cytocentrifuge preparations are helpful. One sample is stained with a Romanowsky-type stain, and the rest can be reserved, if needed, for immunocytochemical studies for lymphocyte surface markers.9 So-called cell blocks are especially useful as adjuncts to the “cytologic” preparations listed previously. To prepare a cell block, the sediment is wrapped in filter paper, placed in a cassette, embedded in paraffin, and cut and stained in the manner of histologic sections. Before placing it in a cassette, however, it is helpful to coagulate the sediment; one common way is to add a few drops of plasma and several drops of a thrombin solution,10–12 but other methods are available,13 including an automated system called Cellient (Hologic, Inc., Bedford, Mass.).14 Clotting the specimen with drops of plasma and thrombin does not disperse the diagnostic cells as does a spontaneously formed clot, but rather congeals the sediment into a compact mass. If the fluid was not heparinized and clots are present, they should be removed and placed in cassettes for processing as cell block material. Using more than one preparation method for effusions improves sensitivity for the detection of malignancy.15 A common preparation combination is one thinlayer slide and a cell block. Cell block sections are especially useful for special stains and immunohistochemistry because of the ease with which multiple duplicate slides can be prepared, the relative absence of obscuring background staining, and the standardization of the preparation for control slides.16 Cell blocks also make for excellent morphologic comparison with histopathologic sections (when, for example, the patient has had a prior breast biopsy) because they are fixed and stained in an identical manner. In some laboratories, an unfixed wet smear stained with toluidine blue is prepared first to identify any fluid that contains large numbers of malignant cells. It is helpful to separate such fluids from the routine staining cycle to prevent cross-contamination.12 Leftover fluid is stored in the refrigerator in case additional slides are needed. Fresh fluid is sometimes useful for other studies such as flow cytometry,17–19 electron microscopy,20 and cytogenetic or molecular genetic analysis.21–23 General categories like “no malignant cells identified” and “positive for malignant cells” are commonly used to report results because they succinctly and unambiguously communicate an interpretation.24 Inconclusive findings—when abnormal cells are too poorly preserved or too few to support a definite diagnosis of malignancy—are commonly reported as “atypical cells present” (connoting a low degree of suspicion) or “suspicious for malignancy” (connoting a high degree of suspicion). Suspicious diagnoses occur in about 5% of specimens.25,26 In this situation, if the patient does have a malignancy involving the serosal cavity, fluid is likely to reaccumulate, and the subsequent specimens may be diagnostic of malignancy. Criteria for the adequacy of an effusion specimen have not been established.24 Cytology is more sensitive than blind biopsy for detecting serosal malignancy (71% versus 45%),27 presumably because fluid provides a more representative sample. Estimates of the sensitivity of cytology for diagnosing serosal malignancy range from 58% to 71%.26,27 The cancer detection rate by cytology is increased by 2% to 38% when multiple sequential specimens are examined.25,28,29 This still leaves a substantial false-negative rate. Thoracoscopy is the procedure of choice for patients with a strong clinical suspicion of pleural disease but a negative cytology result.30 The specificity of a cytologic diagnosis is very high: False-positive diagnoses occur in less than 1% of cases.25,31 When they occur, false-positive and false-suspicious diagnoses are caused by mesothelial cell atypia in the setting of pulmonary infarction,27 tuberculosis,25 chemotherapy,32 acute pancreatitis,31,32 ovarian fibroma25 and cirrhosis.31 In children, false-positives result from misinterpreting benign lymphoid cells as lymphoma or neuroblastoma.33 • confirming malignancy when morphology alone is equivocal • distinguishing adenocarcinoma from mesothelioma • screening an effusion for lobular breast cancer • establishing the primary site of a malignant effusion; a patient with: • assessing receptor status (e.g., HER2) for patients with breast and gastric cancers The circumstances outlined above represent common applications for immunohistochemistry. Antibodies against carcinoembryonic antigen (CEA), B72.3, and a number of other markers have high sensitivity and specificity for malignancy and are extremely useful in a variety of settings, particularly for resolving cases that are cytologically equivocal.34 Detailed discussion of specific applications is found in the sections that follow. Benign effusions contain mesothelial cells, histiocytes, and lymphocytes in varying proportions. Because some bleeding is common during specimen collection, red and white blood cells are common contaminants. Mesothelial cells can be sparse or numerous in benign effusions (Fig. 4.1). They are mainly dispersed as isolated cells or occasional small clusters. Large clusters composed of more than 12 cells are highly unusual in benign effusions. Binucleation and multinucleation are common, and mesothelial cells in mitosis can be seen in benign effusions. The dense cytoplasm reflects the abundance of tonofilaments, and the clear outer rim (“lacy skirt” or “halo”) corresponds to long, slender microvilli, better visualized with electron microscopy. Two or more mesothelial cells in groups are often separated by a narrow space or “window.” Less commonly, mesothelial cells have one or more cytoplasmic vacuoles. Figure 4.1 Mesothelial cells. With acute or chronic injury, mesothelial cells undergo hyperplasia and hypertrophy and can have significant nuclear atypia, but they remain predominantly dispersed as isolated cells. Such “reactive” mesothelial cells generally comprise a spectrum of cells that range from normal to atypical, with variation in nuclear size, a coarse chromatin texture, irregular nuclear contours, or prominent nucleoli (Fig. 4.2). Figure 4.2 Reactive mesothelial changes (peritoneal fluid, cirrhosis). Malignant mesothelioma should be considered if there is marked atypia, particularly if the cells are much larger than normal, or if the fluid contains numerous clusters of 12 or more mesothelial cells, even if the cells themselves are not particularly atypical. Such large groups are uncommon in benign effusions. Clinical correlation is important because it may account for the atypia; some medical conditions, including anemia, cirrhosis, lupus, pulmonary infarction, renal failure, and acquired immunodeficiency syndrome (AIDS),35 are notorious causes of mesothelial atypia. On the other hand, if the patient has a large, unexplained, unilateral effusion, particularly with radiographic evidence of pleural thickening, additional evaluation (pleural biopsy, cytogenetics), should be considered to exclude mesothelioma.21–23 Metastatic malignancy should be considered when a population of cells is identified that is morphologically distinct from the mesothelial cells, histiocytes, and lymphocytes. In a minority of malignant effusions, a second population of cells is not evident. This is particularly true with lobular carcinoma of the breast and melanoma, the cells of which mimic normal histiocytes or mesothelial cells. Special stains are then needed to resolve the case. Some effusions contain abundant histiocytes (Fig. 4.3A). A particularly marked histiocytic reaction to irritation of the serosal surfaces has been termed nodular histiocytic/mesothelial hyperplasia.36,37 This is a nonspecific chronic inflammatory reaction that should not be misconstrued as a malignancy in cytologic or histologic specimens.37 When abundant, histiocytes can form aggregates on smears and liquid-based preparations,37 and they tend to sediment together in cell block preparations, forming masslike aggregates that mimic malignancy. Immunohistochemistry can be useful to distinguish histiocytes from mesothelial cells and metastatic carcinoma: Histiocytes are immunoreactive for CD68 and CD163, and negative for keratin proteins (Fig. 4.3B); the reverse is true for mesothelial cells and metastatic carcinoma. Figure 4.3 Histiocytes (pleural fluid, congestive heart failure [CHF]). In many benign disorders, effusions give a nonspecific cytologic picture. Thus, pleural fluid in CHF or pulmonary infarction is morphologically indistinguishable from pericardial fluid caused by renal failure and peritoneal fluid due to cirrhosis. Fortunately, the features of some benign conditions are sufficiently characteristic to narrow the differential diagnosis or even indicate the specific etiology. To give a very unusual example, finding undigested meat and vegetable matter in pleural fluid strongly suggests esophageal rupture (Boerhaave’s syndrome).38 A pleural effusion is considered “eosinophilic” when eosinophils account for 10% or more of the nucleated cells present. Between 5% and 16% of exudative effusions are eosinophilic effusions.39 The most common causes are pneumothorax and hemothorax.30 The introduction of air or blood into the pleural space, so often the reason behind an eosinophilic effusion, can occur simply with repeated thoracenteses. Less common causes include drug reactions, parasitic infections, pulmonary infarction, and the Churg-Strauss syndrome.30,40 In about one third of cases the origin remains obscure.41 Most cases resolve spontaneously. Eosinophilic pericardial and peritoneal effusions are less common than eosinophilic pleural effusions. Cytologic preparations are usually cellular and remarkable for a high concentration of eosinophils. On alcohol-fixed Papanicolaou-stained slides, the defining “eosinophilic” cytoplasmic granules are either orangeophilic or pale green and inconspicuous, and the cells are identified more on the basis of their bilobed nuclei (Fig. 4.4). The granules are brightly eosinophilic on cell block preparations stained with hematoxylin-eosin (H & E), however, and on air-dried Romanowsky-stained slides. Charcot-Leyden crystals (see Fig. 2.11) are present in some cases and, curiously, are more common in fluids that have been refrigerated for more than 24 hours.42 Figure 4.4 Eosinophilic pleural effusion. A pleural effusion consisting mostly of small lymphocytes is a relatively common but nonspecific finding (Fig. 4.5). Cytologic preparations are often highly cellular and composed almost exclusively of dispersed small lymphocytes.43 Mesothelial cells and histiocytes are either conspicuously absent or present in only small numbers. Figure 4.5 Lymphocytic pleural effusion. Despite the absence of malignant cells, a malignancy is a common cause of a lymphocytic effusion. The malignancy may be nearby (e.g., in the lung) and may be obstructing lymphatic outflow but may not have spread to the pleural surfaces. Alternatively, a pleural malignancy may be evoking a peritumoral lymphocytic response, but the tumor itself is not shedding cells into the effusion.36 It is not uncommon for the initial pleural fluids in patients with a pleural mesothelioma to consist only of lymphocytes.44 An effusion is very rarely the initial manifestation of a lymphoid malignancy. Thus, it is not cost-effective to evaluate every lymphocytic effusion consisting of mostly small round lymphocytes by flow cytometry or immunocytochemistry. On the other hand, if the patient is known to have a lymphoma or thymoma, an immunophenotypic workup is justified to exclude pleural involvement (Fig. 4.6 A-D). Figure 4.6 Metastatic thymoma, type B2 (pleural effusion). The diagnosis of tuberculosis can be confirmed by microbiologic studies or pleural biopsy, which reveals caseating granulomas and acid-fast organisms. The differential diagnosis includes other benign effusions of nontuberculous origin, as in patients after coronary artery bypass surgery.30 Less than 5% of patients with rheumatoid arthritis develop pleural involvement by their disease. In almost all cases, joint disease precedes the development of pleuritis, but occasionally pleuritis precedes or is synchronous with the onset of joint disease.45,46 The pleural effusion can be unilateral or bilateral, and some patients have a synchronous pericardial effusion. Radiographic studies reveal pulmonary nodules in a minority of patients; presumably, these are rheumatoid nodules. The effusion can last for days, months, or sometimes years. The cytologic picture is so characteristic that it has been termed pathognomonic.45 Examination of pleural fluid, therefore, can be extremely useful to confirm the diagnosis of rheumatoid pleuritis and exclude the possibility of coincident disease, especially a malignancy. Cytologic preparations are sparsely or moderately cellular. An abundant granular material dominates the picture (Fig. 4.7A). It can stain green, pink, red, or orange with the Papanicolaou stain, and it aggregates into small and large clumps with irregular edges. Large, islandlike masses can be appreciated in cell block material. The predominant cell is the macrophage, which is round or spindle-shaped; multinucleated macrophages are seen in most but not all cases (see Fig. 4.7A and B). Lymphocytes and polymorphonuclear leukocytes may be seen. Mesothelial cells are noticeably absent. Figure 4.7 Rheumatoid pleuritis. The characteristic cell is the lupus erythematosus (LE) cell, a neutrophil or macrophage that contains an ingested cytoplasmic particle called a hematoxylin body. The hematoxylin body may be green, blue, or purple with the Papanicolaou stain and magenta with Romanowsky-type stains, and has a glassy, homogeneous appearance (Fig. 4.8). Filling the cytoplasm of the neutrophil or macrophage, it often pushes the nucleus to one side, indenting it into a crescentlike shape. Hematoxylin bodies are thought to represent degenerated nuclei. Similar cells that contain ingested nuclei with a visible chromatin structure (rather than the glassy, structureless hematoxylin body) are called tart cells after the patient in whom they were first described. Figure 4.8 Hematoxylin body (lupus pleuritis). LE cells are present in just 27% of effusions in patients with SLE, and only in those with a known diagnosis of SLE.47 Most viral pneumonias associated with a pleural effusion result in a nonspecific cytologic picture. The cytopathic changes characteristic of the herpesviruses and cytomegalovirus (CMV) are rarely seen in serous effusions. Although fungal infections are common in immunocompromised patients, organisms are rarely seen in pleural, pericardial, and peritoneal fluids. Candida species, Cryptococcus neoformans, Coccidioides immitis, Blastomyces dermatitidis, and Aspergillus niger have been described in fluids in rare instances.12 Pneumocystis jirovecii has been identified in pleural and peritoneal effusions from immunocompromised patients.48–50 Papanicolaou stains show foamy exudates similar to those seen in respiratory specimens. The trophozoites measure 2.5 to 5.0 μm and have pale cytoplasm and a dotlike nucleus. They may be intracellular (within macrophages) or extracellular, and are well seen on air-dried preparations stained with a Romanowsky-type stain. Cyst forms measure 4 to 7 μm and can be seen with special stains like the methenamine silver stain. Some tumors have a greater tendency than others to spread to the pleura, pericardium, or peritoneum. The most common are listed in Table 4.1. In children, the most common cause of a malignant pleural or peritoneal effusion is non-Hodgkin lymphoma.33 TABLE 4.1 MOST COMMON TUMORS THAT CAUSE MALIGNANT EFFUSIONS, BY SITE AND GENDER∗ ∗Data from: Sears D, Hajdu SI. The cytologic diagnosis of malignant neoplasms in pleural and peritoneal effusions. Acta Cytol 1987;31: 85-97; and Johnston WW. The malignant pleural effusion: a review of cytopathologic diagnoses of 584 specimens from 472 consecutive patients. Cancer 1985;56: 905-909. Most patients with a malignant effusion have a previously documented primary neoplasm. In some cases, however, a malignant effusion is the first manifestation of an occult malignancy. Lung cancer is the most common occult primary in women and men who present with a malignant pleural effusion. It is extremely uncommon for breast cancer to manifest itself initially as a malignant effusion.29,51,52 The most common occult sources of a malignant peritoneal effusion are gastrointestinal and pancreatic cancer in men and ovarian cancer in women.52,53 Other tumors that can manifest as a malignant effusion include lymphoma, melanoma, and mesothelioma.52 In some patients, the primary site is never discovered.29,52 Malignant cells in pleural, pericardial, or peritoneal fluid betoken a grim prognosis. The median survival for patients with a positive pleural or peritoneal effusion is less than 6 months.54 Certain tumors, like estrogen-positive breast cancers and well-differentiated mucinous adenocarcinomas of the appendix, have a slightly better prognosis. Survival is improved in some patients with therapy targeted against the molecular profile of the cancer.55 Systemic chemotherapy fails to alleviate most recurrent malignant effusions, with a few notable exceptions (e.g., those caused by lymphoma and small cell lung cancer). Because most malignant pleural effusions recur and impede respiration, chest tube placement or pleurodesis (sclerosis of the pleural cavity by injecting talc, doxycycline, or bleomycin) is often performed as a palliative measure.4 For patients with recurrent malignant ascites, palliative treatment may consist of either repeated paracenteses, intraperitoneal chemotherapy, placing a drainage catheter, or implanting a peritoneovenous shunt (usually into the superior vena cava).4,54 Surprisingly, there is no evidence that disseminating tumor cells via a peritoneovenous shunt decreases survival.4 The various treatment options have their advantages and disadvantages; selecting the best treatment option focuses on the patient’s desires and improving the quality of life. Malignant cells in cell block sections are frequently situated in lacunae (Fig. 4.9). These clear spaces surrounding individual cells or groups of cells are seen in 75% of cell blocks of malignant effusions, mostly adenocarcinomas, but the finding is not specific; lacunae are also seen in one third of benign effusions.56 Lacunae are helpful in locating potentially abnormal cells at low magnification, but inspection at high magnification is needed for definitive diagnosis. Figure 4.9 Cell block lacunae (pleural fluid). Diffuse malignant mesothelioma (for simplicity, mesothelioma) accounts for less than 2% of malignant effusions.36,57 Strongly linked in most cases to asbestos exposure, it arises most commonly in the pleura and less commonly in the peritoneum; primary tumors of the pericardium or tunica vaginalis of the testis are rare. The latency (time from first asbestos exposure to clinical disease presentation) is extremely long, with an average of 30 to 40 years. The peak incidence in the United States appears to have happened in the 1990s, but cases are still increasing in other countries such as Great Britain and Australia.36 Malignant mesothelial cells grow as multiple plaques that coalesce into larger nodules visible radiographically as a thickening of the pleura. Histologically, these tumors are classified as epithelioid, sarcomatoid, desmoplastic, or biphasic types.58 The epithelioid type comes in a variety of variant histologic patterns—tubulopapillary, adenomatoid (microglandular), sheetlike, deciduoid, small cell, and clear cell—but mixed patterns are common, and some of these are rare.36,58 Most mesotheliomas are, in fact, well-differentiated tumors and cytologically remarkably, deceptively bland. Mesotheliomas, like benign mesothelial cells, are immunoreactive for cytokeratins, desmin, calretinin, Wilms tumor protein 1 (WT1), and D2-40. Common symptoms are chest pain and shortness of breath. Establishing the diagnosis is not always straightforward, with a median time from the onset of symptoms to diagnosis of 8 weeks.44 Most patients have an effusion, usually unilateral, at the time of presentation. A positive mesothelioma effusion is often grossly described as having the color and consistency of honey. When suspicious and positive results are combined, the sensitivity of effusion cytology for the diagnosis of mesothelioma is only 32%.44 Only the epithelioid and mixed (biphasic) types of mesothelioma are likely to exfoliate malignant cells; the pure sarcomatoid and desmoplastic types rarely exfoliate. When the malignant cells exfoliate, the most recognizable cytologic pattern is characterized by numerous large clusters (morulae) (Fig. 4.10A). The clusters are composed of up to hundreds of cells that are recognizably mesothelial in origin, with round nuclei, prominent nucleoli, and dense cytoplasm with a pale rim. The morulae have a knobby, scalloped contour (“mulberry clusters”), and some show branching (Fig. 4.10B). In most cases, the malignant mesothelial cells are larger than normal mesothelial cells, sometimes markedly so. Cytoplasm is abundant in most cases, and therefore the nuclear-to-cytoplasmic ratio is often deceptively normal (Fig. 4.10C), but cytoplasm can be scant in some cases (Fig. 4.10D). Occasionally, microvilli can be appreciated (Fig. 4.11). Nuclear atypia is mild in most cases. On cell block sections, the clusters are a solid mass of cells (see Fig. 4.11), or they may contain a collagenous or acid mucopolysaccharide core (Fig. 4.12). Figure 4.10 Malignant mesothelioma (pleural fluid).
Pleural, Pericardial, and Peritoneal Fluids
Specimen Collection, Preparation, and Reporting Terminology
Accuracy
When to use immunocytochemistry for effusions
Benign Elements
A, Many characteristic features of mesothelial cells are seen here: the peripheral lucent zone, or “lacy skirt” (arrow); the dense perinuclear zone; the occasional binucleation; and the slitlike separation (“window”) between adjacent cells. A few histiocytes (arrowheads) with folded nuclei and vacuolated cytoplasm are also present (Papanicolaou stain). B, Peripheral halos are well seen in this cell block section. Note also the large multinucleated mesothelial cell, a nonspecific finding (hematoxylin-eosin [H & E] stain).
Some benign fluids contain a population of moderately enlarged mesothelial cells with large, hyperchromatic, irregular nuclei (Papanicolaou stain).
A, Like mesothelial cells, histiocytes are usually isolated cells, but centrifugation for cell block sections compresses them into large groups. Compare the histiocytes, which have an oval or folded nucleus, with the mesothelial cell (arrow) (hematoxylin-eosin[H & E] stain). B, Only the mesothelial cell is immunoreactive for cytokeratins.
Non-Neoplastic Conditions
Eosinophilic Effusions
Numerous eosinophils in pleural fluid are more commonly associated with benign conditions like a pneumothorax (as in this case) or hemothorax (Papanicolaou stain).
Lymphocytic Effusions
The specimen consists almost exclusively of small lymphocytes with round nuclei and condensed chromatin. This finding is nonspecific (Papanicolaou stain).
A, The specimen looks like a nonspecific lymphocytic effusion, but the patient had a history of a thymoma (Papanicolaou stain). B, The cell block confirms the presence of numerous small lymphocytes (hematoxylin-eosin [H & E] stain). C, Numerous lymphocytes are positive for Tdt (terminal deoxytransferase), a marker of thymic lymphoid cells. D, A cluster of cells shows strong immunoreactivity for p63, a marker of squamous differentiation that is usually negative in mesothelial cells.
Rheumatoid Pleuritis
A, Scattered multinucleated histiocytes and clumped granular debris in the background are characteristic of pleural fluids in patients with rheumatoid pleuritis (Papanicolaou stain). B, A pleural biopsy has the appearance of an “opened-out” rheumatoid nodule, with epithelioid histiocytes, giant cells, and fibrinoid debris lining the pleural space (hematoxylin-eosin [H & E] stain).
Lupus Pleuritis
The lobes of the nucleus are pushed against the side of the neutrophil by a large, homogeneous, intracytoplasmic body (Romanowsky stain).
Other Non-Neoplastic Conditions
Malignant Effusions
Site
Men
Women
Pleural
lung
lymphoma/leukemia
gastrointestinal tract
sarcoma
mesothelioma
genitourinary (kidney, prostate, bladder)
melanoma
breast
lung
lymphoma/leukemia
ovary
gastrointestinal tract
endometrium
sarcoma
mesothelioma
Peritoneal
lymphoma/leukemia
gastrointestinal tract
pancreas
lung
sarcoma
prostate
melanoma
germ cell tumors
mesothelioma
ovary
breast
endometrium
stomach
lymphoma/leukemia
colon and rectum
pancreas
mesothelioma
In cell block sections, malignant cells are often situated in an empty space (lacuna); the reason for this artifact is unknown. It is commonly seen with adenocarcinomas, rarely with lymphomas and melanoma (hematoxylin-eosin [H & E] stain).
Primary Tumors
Diffuse Malignant Mesothelioma
Cytomorphology of mesothelioma
A, Solid, morulelike spheres, some of them elongated, are composed of cells that resemble normal mesothelial cells. A fluid composed of many large clusters is virtually always malignant (Papanicolaou stain). B, A branching pattern is seen in some cases. Note the knobby contours (Papanicolaou stain). C, In most mesotheliomas, the nuclear-to-cytoplasmic ratio of normal mesothelial cells is recapitulated (Papanicolaou stain). D, In other cases, the nuclear-to-cytoplasmic ratio is significantly increased (Papanicolaou stain).
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Pleural, Pericardial, and Peritoneal Fluids
Cytomorphology of mesothelial cells
Differential diagnosis of reactive mesothelial cells
Cytomorphology of histiocytes
Differential diagnosis of a lymphocytic effusion
Cytomorphology of rheumatoid pleuritis
Tips for detecting malignant cells in effusions