Introduction to the second edition of ‘Diagnostic Cytopathology of Serous Fluids’ as CytoJournal Monograph (CMAS) in Open Access

Histology

The mesothelium forms a parietal and visceral layer in each cavity, where it is reflected over the organs therein. It consists of a flat monolayer of mesothelial cells, which have a tendency to undergo hypertrophy and hyperplasia secondary to various stimuli, usually resulting in a somewhat cuboidal appearance [Figure 2]. Such ‘reactive’ mesothelial cells frequently exfoliate into serous effusions. Although derived from mesoderm, mesothelial cells possess many of the morphologic and biologic features of epithelial cells [see Figure 2].

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Figure 2:

Histology of serous lining (inguinal hernia sac). The mesothelial cells lining the fibrous tissue are flat (1). Focal reactive changes are seen as hypertrophy of some cells, which assume a cuboidal contour (2,3). [a–d, HE stain (a, 10×; b–d, 100×).]

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Underlying the mesothelial cells of each serous cavity is a thin layer of fibrous connective tissue with a varying proportion of adipose tissue, small blood vessels, and lymphatics. The lymphatic vessels open on to the surface lining of the serous cavities through gaps (stoma) between the mesothelial cells, which provides continuity between the lymphatic system and the serous cavities.^1,2 The lymphatics are a significant component of the system for absorption of fluid in serous cavities. Any homeostatic imbalance in this system results in accumulation of fluid in serous cavities leading to the effusions. It is of interest to note that the recently reported immunomarkers for lymphatic endothelium, such as D2-40 and podoplanin, have been reported to be immunoreactive in mesothelial cells also.^[3–5] This suggests a relationship between mesothelial cells and lymphatic endothelial cells.

The serous cavities may be affected by a variety of processes, including inflammation, hepatic cirrhosis, congestive heart failure and other hemodynamic aberrations, and metastatic neoplasms. These processes often elicit reactive changes in mesothelial cells. The damaged mesothelium can be replaced by differentiation of the mesenchymal cells from the underlying stroma [see Figure 2]. The reactive mesothelial cells are hypertrophied and appear somewhat cuboidal with enlarged nuclei and conspicuous nucleoli [see Figure 2]. They may show variation in nuclear size and shape, multinucleation, and increased nuclear/cytoplasmic ratios. All these features are best observed in cytologic preparations Figure 3 and 4].

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Figure 3:

Mesothelial cells (peritoneal fluid): show outer faintly stained ectoplasm (1) with inner denser endoplasm (2) rich in intermediate filaments. The nucleus is usually central or near central (b), but may be eccentric (c). Nucleoli are readily observed. The vacuolation generally begins at the periphery in ectoplasm (1). [b,c, PAP-stained Autocyte Prep smear (b,c, 100× zoomed).]

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Figure 4:

Mesothelial cell (pleural fluid): shows outer ectoplasm, which is denser than the inner endoplasm. The nucleus is central to slightly eccentric but not touching the cell periphery. The cell margin shows blebs and is ruffled. [DQ-stained Cytospin smear (100× zoomed).]

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General cytology (with Papanicolaou and Diff-Quik stains)

Serous effusions may contain a variety of non-neoplastic cells, including mesothelial cells, macrophages, and other blood-derived cells [Table 1], together with other entities such as psammoma bodies and various incidental cellular and non-cellular elements [Table 2].

Mesothelial cells

After exfoliation, mesothelial cells round up and appear polyhedral due to the surface tension of the surrounding effusion fluid. They may be seen as singly scattered cells [Figures 3 and 4] or in small cohesive clusters and sheets [Figures 6, 8, 11]. The cells are of various sizes and may be round to oval. The morphology of mesothelial cells can be evaluated in Papanicolaou (PAP) and Diff-Quik (DQ) stained smears. In general, the PAP stain allows better evaluation of nuclear details, while the DQ stain highlights cytoplasmic details [Table 3].

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Figure 5:

Mesothelial cells (a -c) versus adenocarcinoma cells (d -f) with eccentric nuclei. A thin rim between nuclear border and cell border (1) is seen in mesothelial cells. In comparison, the nuclear border in adenocarcinoma cells touches the cell border without a significant cytoplasmic rim (2). [PAP-stained Direct smear (b, e, 100× zoomed); PAP-stained SurePath Prep smear (c, f, 100× zoomed).]

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Figure 6:

Mesothelial cells versus adenocarcinoma cells. (a) Mesothelial cells with central to eccentric nuclei. A thin cytoplasmic rim separates the nuclear border from the cell border (red arrow 1). (b) In comparison, the adenocarcinoma cells with eccentric nuclei appose the cell border (blue arrow 2). [a,b, DQ-stained Cytospin smear (a,b, 100× zoomed).]

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Figure 7:

Multinucleated mesothelial cell: a mesothelial cell with three nuclei (arrows), which may vary in size. [PAP-stained SurePath Prep smear (100×).]

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Figure 8:

Monolayer of mesothelial cells in pelvic washings which may fold on itself (Pap stain, ×200). (Right) Strip of mesothelium seen as a “string of pearls” in a cell-block preparation (Cell-block section H and E, ×200).

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Figure 9:

Mesothelial windows (arrows): reactive mesothelial cells, pleural fluid. [DQ-stained Cytospin smear (a–d 100μ; inset of b, 100× zoomed).]

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Figure 10:

Mesothelial windows (arrows): reactive mesothelial cells, pleural fluid. [PAP-stained SurePath Prep (100×; inset, 100× zoomed).]

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Figure 11:

Monolayered flat sheet of mesothelial cells: may resemble squamous metaplastic cells. The spaces between mesothelial cells, mesothelial windows, are common (red arrows). Microvilli prevent the adjacent cells from apposing their cell borders with each other. Depending on many variables, the mesothelial windows may be subtle to very wide (peritoneal washing). [PAP-stained Cytospin smear (100×).]

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In cytologic preparations, mesothelial cells are usually about 15–30 µm in diameter (1.5–2 times the size of neutrophils), but they may vary significantly and may range up to 50 µm in diameter. They appear larger in DQ-stained air-dried smears than the wet-fixed shrunken cells in PAP-stained smears [see Figure 13]. In PAP-stained preparations, the perinuclear zone, with its higher density of intermediate filaments, shows relatively dense staining endoplasm with a surrounding narrow zone of pale ectoplasm associated with microvilli [see Figure 3]. In DQ-stained preparations, the endoplasm is lightly stained with peripheral darker ectoplasm [see Figure 4]. The cell borders are round to oval but usually have ruffled surfaces with blebs. • In general, the two-zone staining characteristic of mesothelial cells is discerned better in DQ-stained preparations.

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Figure 12:

Macrophages: mesothelial and histiocytic macrophages show morphological overlap. a–d are morphologically suggestive of mesothelial macrophages; e and f favor histiocytic macrophages (pleural fluid). [a–f, DQ-stained Cytospin smear (100× zoomed).]

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Figure 13

Reactive mesothelial cell (RM) with inflammatory cells: lymphocyte (L), neutrophil (N), and eosinophil (E) (pleural fluid). [a, PAP-stained SurePath Prep; b, DQ-stained Cytospin smear (a,b, 100×; L, N, E, 100× zoomed).]

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Although this typical appearance of mesothelial cells helps to distinguish them from other cells in effusions, including malignant cells, it is not specific for mesothelial cells. Nonmesothelial neoplasms such as malignant melanoma and well-differentiated adenocarcinomas of the breast and ovary may demonstrate some morphologic overlap with reactive mesothelial cells [Figures 5].

The nuclei of mesothelial cells are usually centrally placed or slightly off center, but may be distinctly eccentric. Even when they are eccentric, their nuclear membranes do not touch the cell border. Careful examination shows a narrow rim of cytoplasm adjacent to the eccentric nucleus [see Figure 5]. This narrow rim, which is better highlighted in DQ-stained preparations, is related to the microvilli on the surface of mesothelial cells [see Figure 6].

Binucleation and multinucleation of reactive mesothelial cells is frequent, especially in non-malignant effusions. It is not uncommon to see variation in the sizes of multiple nuclei in the same cell [Figure 7]. Nucleoli are usually seen and may be prominent [see Figure 3]. However, huge macronucleoli equal to one-third the size of the nuclear diameter associated with some malignancies such as melanoma, hepatocellular carcinoma, germ cell tumors, and prostatic adenocarcinoma are rarely found in reactive mesothelial cells. The chromatin is usually finely granular (powdery) with various degrees of chromasia. Many of these nuclear details can also be seen in DQ-stained smears, but malignancy-related hyperchromasia and chromatin details cannot be evaluated properly in DQ-stained smears [see Figure 4].

With DQ staining, mesothelial cell cytoplasm may not always show the two zones. As the mesothelial cells imbibe water from the effusion fluid, their cytoplasm may acquire a foamy macrophage phenotype with pale vacuolated cytoplasm [Figures 12]. The degree of vacuolization is directly proportional to the duration that the cells remain in the fluid medium. As the effusion becomes chronic, the cytoplasmic vacuoles become larger. The cytoplasmic vacuoles of mesothelial cells are usually small and located at the periphery of the cells, but they may be randomly distributed or even be central with nuclear overlap [see Figure 12]. A single, large, cytoplasmic vacuole displacing the nucleus may cause a mesothelial cell to resemble a signet ring cell of adenocarcinoma.

Differences between macrophage-like mesothelial cells and histiocytic macrophages, although not of great clinical significance, are difficult to identify by morphology alone. Nuclear morphology may help to make some distinction. Mesothelial cells have round to oval nuclei with smooth contours, whereas histiocytic macrophages typically show bean-shaped (kidney-shaped, reniform) nuclei or with slightly irregular contours [see Figure 12].

• The surfaces of mesothelial cells have numerous, long, slender microvilli, which impart a peripheral rim of pallor in PAP-stained preparations. Microvilli are best seen by electron microscopy (EM). This characteristic feature of mesothelial cells has been applied to distinguish them from other cells such as carcinoma cells.^[11–13] Although the microvilli cannot be seen directly under the light microscope, their presence may be inferred from a thin rim of cytoplasm by the side of an eccentric nucleus [see Figure 5]. This feature, although observed in both types of staining, is more easily recognized with DQ stain. • The swollen microvilli impart ruffled borders and peripheral blebs in DQ preparations [see Figures 4]. In contrast, if the nucleus is eccentric in histiocytic macrophages, it touches to the cytoplasmic membrane without rim of cytoplasm (comparable to that in adenocarcinoma cells with nuclear features of malignancy, better evaluated in PAP stained preparations [Figure 3]).

The microvilli of mesothelial cells may prevent adjacent cells from completely apposing each other, thereby creating a gap between the adjacent cell membranes, which gives rise to the appearance of a space referred to as a mesothelial window [see Figures 9-11]. Depending on many variables, these windows may be subtle or very wide in cytology smears. Such spaces are not specific for mesothelial cell only, but they may be seen in the cell groups of some metastatic cancers in effusions.

The cytoplasm stains light green with a variable degree of intensity and vacuolization in PAP-stained preparations.

• PAP-stained preparations do not highlight the cytoplasm well, giving the impression of less cytoplasmic volume compared with that observed in DQ-stained smears [Figure 10]. The cytoplasm in PAP-stained preparations is less distinct and more transparent. The non-highlighting of cytoplasm associated with PAP staining is enhanced further due to cellular shrinkage in wet fixed preparations; although less distinct, mesothelial windows [Figure 10] and cytoplasmic vacuoles may still be evident in PAP-stained smears.

Nuclear details, however, are better seen in PAP-stained preparations [see Figure 3]. Usually, centrally placed nuclei are typically round to oval with smooth contours (even malignant mesothelial cells may continue to demonstrate round nucleus with regular smooth outlines). As their cytoplasm becomes vacuolated due to phagocytic activity or degenerative changes, the nuclei of these mesothelial cells may be displaced to the periphery of the cell. On close inspection, in most of the cells the nuclei do not touch the outer margin of the cell [see Figure 5a,b,c]. As mentioned previously, this is secondary to the slender bushy microvilli along the periphery of the mesothelial cells . This feature may be applied to distinguish mesothelial cells from histiocytic macrophages and carcinoma cells, which characteristically show peripherally located nuclei touching the cell membrane [see Figure 5d,e,f].

Although mesothelial cells do not proliferate in effusion fluid after exfoliation, they may complete an already started mitotic division. The presence of mitotic figures in effusion cytology may reflect a process in the serosal lining that is capable of causing significant proliferative activity of mesothelial cells in response to the factors responsible for the effusion.

• As is applicable to cytopathologic evaluations in general, the presence of nucleoli and mitotic figures should not mislead the interpreter into making a false interpretation of malignancy. Other general morphologic features of malignancy should be applied to arrive at such an interpretation. Once correctly interpreted as malignant, then the nucleoli and mitotic figures may be considered for further categorization and grading of a neoplasm.

Mesothelial cells produce hyaluronic acid, which, if present, may be seen as magenta-colored intracytoplasmic or extracytoplasmic material in the DQ-stained preparations or as light gray streaks in the background of PAP-stained preparations. This may also be present in the center of small groups of mesothelial cells and may resemble a mucin-containing acinus of adenocarcinoma. Hyaluronic acid demonstrates positive staining with periodic acid–Schiff (PAS) and Alcian blue stains. This staining is lost if the slides with tissue sections are treated with hyaluronidase prior to staining. Hyaluronic acid is not the substrate for diastase and is not digested by it. Consequently, PAS positivity of hyaluronic acid in the sections stained with the commonly used PAS staining method (i.e. PAS staining after treatment with diastase) is not lost.

Mesothelial cells in washings and lavages

Peritoneal washings and lavages are commonly submitted as part of staging procedures for gynecologic cancers.^[2,14] In addition to this, other indications for peritoneal washings include staging of non-gynecologic malignancies (such as Pancreatic, gastric), ruling out occult cancer, and evaluate response to therapy (the “second-look” procedure). Recently peritoneal washings are performed in increasing numbers prior to the prophylactic ovarian and fallopian tube resections in cases with BRCA mutation carriers. Cancers were detected in 2–10% of specimens which may be missed during pathologic evaluation even after processing of the entire specimen^15,16. As recommended by Society of Gynecologic Oncologists Clinical Practice Committee, although not required as the part of risk-reducing prophylactic resection procedures currently, peritoneal washing with cytologic evaluation is considered reasonable until more data on the topic is accumulated^[9c].

In these specimens, the mesothelial cells have a different appearance than those in effusions, which are naturally exfoliated with reactive changes. The mechanically dislodged cells fall into a free-floating configuration in the fluids and are seen as monolayered flat sheets that may resemble sheets of squamous metaplastic cells [see Figure 8 and 11]. Individual mesothelial cells arranged in a jigsaw puzzle pattern have well-defined cytoplasmic borders with distinct slits between some cells. The cells are not round but have angulated rhomboidal/trapezoidal shapes with centrally placed bland nuclei. Some of these sheets of cells may curl and fold onto themselves and give a three-dimensional appearance. Careful evaluation of these aggregates along the periphery helps to decide the true nature of these folded sheets and distinguish them from the three-dimensional balls of proliferation spheres [Figure 17] of neoplastic cell groups. At least some areas along the edges of the group help to confirm the monolayered nature of these aggregates of mechanically stripped sheets of mesothelial cells related to the washing procedure. Contaminants such as collagen spheres,^[17] Müllerian inclusions^[10b] and atypical papillary proliferations^[18] may lead to serious false positive error in the cytologic interpretation of peritoneal/pelvic washings.^[19]

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Figure 14

Hemosiderin in macrophages. Coarsely granular, brown pigment, which is blue-gray in Diff-Quick stained preparation (a,b: Papanicolaou stained direct smear; c,d: Diff-Quick stained direct smear).

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Figure 15:

Megakaryocyte (1) with adjacent mesothelial cell (2) in hemorrhagic pleural fluid. [DQ-stained Cytospin smear, 100×].

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Figure 16:

Psammoma body: round acellular bodies with concentric lamination (peritoneal fluid). [PAP-stained SurePath Prep (100× zoomed).]

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Figure 17:

a through h: Collagen globules (Pap stained ThinPrep, in increasing order of cellularity for the wrapping mesothelial cell layer) i: Collagen globule section (HE stained cell-block section) showing central collagen (c) with peripheral layer of mesothelial cells (arrow).

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Macrophages

Macrophages in effusions may be mesothelial or histiocytic. They may be the predominant cell population in some effusions and have highly variable morphologic appearances in DQ-stained preparations [see Figure 12]. • Mesothelial and histiocytic macrophages are difficult to distinguish from each other by morphology alone. Although usually clinically irrelevant and generally not indicated, immunocytochemistry can distinguish them. Mesothelial macrophages demonstrate immunoreactivity for cytokeratin 7, calretinin (nuclear), D2-40, and membranous immuno-reactivity for HBME-1. Histiocytic macrophages, on the other hand, show immunoreactivity for CD68 (PG-M1 and KP1), CD163, and LCA. Generally, macrophages without a qualifier (as histiocytic or mesothelial) are considered to be histiocytic macrophages.

The histiocytic macrophages are round, with well- to ill-defined cell borders. They are non-cohesive and singly scattered, but may be seen in small, ill-defined, loose clusters with irregular peripheral contours. The nuclear margin of the eccentric nucleus may be closely approximated to the cell membrane. Generally, relatively normochromatic nuclei are kidney-shaped and nucleoli are indistinct [Figure 12 e,f]. Some cells may be multinucleated. In PAP stained preparations, the variably cyanophilic cytoplasm is pale and homogeneous to extensively vacuolated. Some macrophages may show intracytoplasmic waste products or material such as hemosiderin associated with endometriosis, melanin with malignant melanoma, and other components such as erythrocytes, inflammatory cells, nuclear particles, or microorganisms, etc.

Hemosiderin and melanin appear as yellow to brown granular material in Pap stained preparations. However, these pigments appear as gray to blue granular material in Diff Quik stained preparations [Figure 14]. In contrast to this, hematoidin and bile pigment are yellow in both Pap stained and Diff Quik stained preparations.

In comparison, mesothelial macrophages may also have overlapping morphologic features with some subtle differences such as round to oval nuclei (in contrast to reniform nuclei in histiocytic macrophages) and centrally positioned nuclei (rather than peripheral or eccentric nuclei as in histiocytic macrophages) [Figure 14]. If the nuclei of mesothelial macrophages are eccentric, the nuclear margin is usually not in close approximation to the cell border, but shows a narrow rim due to numerous long slender microvilli (in contrast to close approximation to the cell border in histiocytic macrophages). The cell borders are well defined with blebs (in contrast to ill-defined in histiocytic macrophages). Mesothelial macrophages are seen as cohesive groups with a distinct knobby contour (in contrast to non-cohesive ill-defined small loose groups with irregular outlines of histiocytic macrophages; Table 4].

Extensive vacuolization with peripheral displacement of nuclei in some macrophages may resemble adenocarcinoma cells with secretory vacuoles. The mucicarmine stain for mucin on the cell-block sections may help. Macrophages will not demonstrate positive staining, whereas adenocarcinoma cells may show mucin positivity [Figure 22]. However, as a histochemical stain, mucicarmine may show variation in interlaboratory reproducibility, which may compromise sensitivity and specificity of this otherwise simple, economical ancillary test.

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Figure 18:

Because of superficial morphological resemblance, lubricant-debris (arrows) in effusion specimen could be confused with mucin (a&b: Pap stained direct smear; c&d: Diff-Quick stained direct smear). This pit-fall may deepen further with histochemical testing with positivity for Mucicarmin stain (c&d in Figure 20).

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Figure 19:

Abundant lubricant-debris (arrows) in peritoneal washing (should not be confused with mucin).

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Figure 20:

Lubricant-debris (arrows) in effusion specimen (a&b: HE stained cell-block section), which because of superficial morphological resemblance could be confused with mucin. This pitfall may deepen further with histochemical testing with positivity for Mucicarmin stain (c&d).

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Figure 21:

Sampling of pleural lesions: biopsy (a) versus effusion cytology (b). Focal lesions may be missed by biopsy. However, cells exfoliated from any of these focal lesions are pooled in the fluid and should be present in a related effusion or washing (Bx, biopsy).

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Figure 22:

Mucicarmine stain: adenocarcinoma cells are mucicarmine positive (arrow) (peritoneal fluid). [cell-block section, 100×.]

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Blood-derived cells

Depending on the extent of peripheral blood contamination and cause of an effusion, red blood cells, lymphocytes, neutrophils, eosinophils, basophils, histiocytes, and megakaryocytes [see Figure 13, Table 1] may be present in effusions. The morphology of these cells is similar to that in DQ-stained smears of peripheral blood and bone marrow. Due to the conventional approach of evaluating these cells with Romanowsky stains, they are best interpreted in DQ- rather than PAP-stained preparations.

Other entities

In addition to mesothelial cells and inflammatory cells, some structures such as psammoma bodies, collagen balls, and detached ciliary tufts may be present, but usually in washing and cul-de-sac fluids.

Extraneous entities and non-cellular material in serous cavity effusions and washings [see Table 2]

Types of effusions

From the point of view of cytopathology, effusions may be non-neoplastic (secondary to collagen diseases, circulatory system disorders, trauma, inflammation, infection, etc.) or malignant (related to cancers).^[35] Pathophysiologically,^[36] effusions in serous cavities may be categorized as transudates, exudates, or chylous [Table 5].

An effusion confirmed as a transudate usually does not require diagnostic evaluation for malignant cells. But exu-dates generally need cytologic evaluation to determine their cause. In experienced hands, cytologic examination of effusions is better than the biopsy of the serous lining for the diagnosis of malignancy^[35,37–40] [Figure 21]. Because of the focal distribution of the lesions, they may be missed during biopsy of a serous surface. In contrast, an effusion contains cells exfoliated from the entire surface of a serous cavity [see Figure 21]. If consecutive effusions from cancer patients are evaluated, the detection rate for cancer cells is increased further.^[41–43] • Wide variations in morphologic features of the highly versatile mesothelial cells overlap with those of malignant cells. This is one of the main challenges during interpretation of effusion cytopathology. Degenerative changes and poor cellular preservation, superimposed on other technical problems frequently associated with these specimens, add to the difficulty.

Pitfalls associated with cytomorphologic evaluation of nonneoplastic effusions, especially those associated with hepatic cirrhosis, pulmonary infarction, and acute pericarditis, may lead to diagnostic errors. As the reactive changes in the mesothelial cells associated with these conditions overlap significantly with malignant cells, the floridly reactive mesothelial cells in such cases may be misinterpreted as malignant. A conservative approach is recommended when interpreting effusion cytology with such a clinical history.

Malignant effusions

Most recurrent and hemorrhagic effusions are caused by cancer. • A massive bloody effusion in the absence of trauma (and without coagulopathy) is almost always due to cancer. Malignant neoplasms of almost any site of origin, perhaps with the exception of the central nervous system, can cause effusions in serous cavities by direct invasion or metastasis. However, a rare case of involvement of the peritoneal cavity secondary to diffuse leptomeningeal gliomatosis in a patient with a ventriculoperitoneal shunt has been reported.^[44]

In men, carcinoma of lung is the most common cause of malignant pleural effusions, followed by carcinomas of the gastrointestinal tract and pancreas. In women, it is carcinoma of the breast, followed by lung and ovary. Cancers of the gastrointestinal tract, ovary, and pancreas predominate as causes of effusions in the peritoneal cavity.

• In comparison with non-malignant effusions, a malignant effusion will re-accumulate rapidly. However, if the effusion is non-malignant, it may not recur or may take a longer time to do so. If the initial cytologic specimen is suspicious but not conclusive for malignancy, a repeat specimen is easy to obtain. It may lead to a definitive diagnosis. Therefore, cytologic findings that appear worrisome but not diagnostic, it is recommended not to rush and make a definitive diagnosis. Instead, a repeat tap should be requested when the effusion recurs. Adequate quantity (preferably more than 100 ml, up to 1000 ml) of such a repeat specimen should be submitted fresh immediately after collection to avoid the artifacts secondary to degenerative changes, which are usually the predominant cause of initial indeterminate interpretation. Relevant clinical details should be available. • As the number of neoplastic cells in recurrent malignant effusions often increase, with many cohesive clusters the cytologic interpretation of repeat specimen is usually definitive.

Neoplasms associated with malignant effusions may be of epithelial or non-epithelial type. Epithelial neoplasms may be metastatic carcinoma or malignant mesotheliomas. Nonepithelial neoplasms include hematologic neoplasms, melanoma, and sarcomas. With the exception of hematologic neoplasms such as lymphoma, non-epithelial neoplasms are rare in effusions.

Pediatric malignant effusions

A series of 226 effusions from 146 patients under the age of 18 years over a 40-year period showed that pleural effusion is the most frequent malignant effusion in children:^[45] 47% (66/139) of pleural fluids were positive for neoplastic cells, followed by 23% (15/65) of ascitic fluids, 27% (4/15) of peritoneal washings, and 43% (3/7) of pericardial fluids. Lymphoma and leukemia (52%) were the commonest associated primary neoplasms, followed by neuroblastoma (14%), Wilms’ tumor (9%), gonadal and extragonadal germ cell neoplasms (8%), bone and soft tissue sarcomas (7%), epithelial neoplasms (5%), Ewing’s sarcoma (2%), and other neoplasms (3%).^[45]

Another study^[46] with similar results reported that:

• most pediatric effusions are benign

• malignant pediatric effusions are usually secondary to small round cell neoplasms, mostly lymphoma and leukemia

• distinguishing neoplasms of the small cell type from mononuclear inflammatory cells is the major diagnostic pitfall

• the role of peritoneal washings in the pediatric group is similar to that in adults.