The intrathoracic and intraperitoneal organs are covered by a single layer of mesothelial cells, which is continuous with the lining of the thoracic and peritoneal cavities. The potential space between the two layers of epithelium contains a small amount of lubricating fluid.
Serous fluid lies between the membranes lining the body cavities(parietal) and those covering the organs within the cavities(visceral).
Production and reabsorption are normally at a constant rate. They are influenced by
Changes in osmotic and hydrostatic pressure in the blood.
Concentration of chemical constituents in the plasma
Permeability of blood vessels and membranes.
An accumulation of fluid, called an effusion, results from an imbalance of fluid production and reabsorption. This fluid accumulation in the pleural, pericardial, and peritoneal cavities is known as serous effusion.
6. • The intrathoracic and intraperitoneal organs are
covered by a single layer of mesothelial cells, which is
continuous with the lining of the thoracic and peritoneal
cavities. The potential space between the two layers of
epithelium contains a small amount of lubricating fluid.
•Serous fluid lies between the membranes lining the
body cavities(parietal) and those covering the organs
within the cavities(visceral).
COMPOSITION AND FORMATION
7. • Production and reabsorption are normally at a
constant rate. They are influenced by
– Changes in osmotic and hydrostatic pressure in the
blood.
– Concentration of chemical constituents in the plasma
– Permeability of blood vessels and membranes.
• An accumulation of fluid, called an effusion,
results from an imbalance of fluid production
and reabsorption. This fluid accumulation in the
pleural, pericardial, and peritoneal cavities is
known as serous effusion.
9. Histology of the Epithelium
• Serous membranes consist
of connective tissue that is
normally lined by a single
layer of mesothelial cells
• 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)
mesothelium
Image courtesy of Boston University
peritoneal cavity
Connective tissue of serosa
10. Biologic nature of effusion
• Effusions are classified into four categories
– Hydrostatic
– Infectious
– Noninfectious inflammatory
– Malignant
• Each category can be one of two types
– Transudate
– Exudate
11. Hydrostatic Effusions
– Due to imbalance of intravascular pressure
resulting in increased flow of plasma into body
cavities
– Higher fluid to cell ratio
– Low protein level
– Cardiac failure is common cause
12. Infectious Effusions
– Due to direct effects of organism or as by-
product of inflammation
– Varying types of inflammatory cells can be
present
– Cultures and/or gram and acid fast stains may
be useful to identify an organism
13. Noninfectious Inflammatory
Effusions
– Due to autoimmune conditions or reaction to a
stimulus
– Autoimmune conditions include rheumatoid
arthritis and systemic lupus
– Reactive conditions include tissue necrosis or
radiation therapy
14. Malignant Effusions
– Due to a primary tumor (such as
mesothelioma) or a metastatic tumor
– Patient history is extremely helpful in
rendering a diagnosis
– Knowledge of the appearance of the fluid is
also helpful (cloudy, bloody, partially clotted)
17. FEATURE TRANSUDATE EXUDATE
Definition Filterate of blood plasma
without changes in endothelial
permeability.
Due to physiomechanical
factors.
Oedema of inflamed tissue
associated with increased
vascular permeability,
damage to serous
membranes.
Character Non-inflammatory oedema Inflammatory oedema
Grossly Typically clear, pale yellow fluid Usually cloudy, yellow or
bloody
Protein content Low, no tendency to coagulate
as mainly albumin, no
fibrinogen.
High, readily coagulates due
to high content of fibrinogen.
Glucose content Same as plasma Low
Specific gravity Low High
pH >7.23 <7.23
LDH Low High
Effusion LDH/Serum LDH ratio <0.6 >0.6
Cells Few cells, mainly mesothelial
cells and cellular debris
Many cells, inflammatory as
well as parenchymal.
18. Light's Criteria
• If at least one of the following three criteria is
present, the fluid is virtually always an
exudate
• If none is present, the fluid is virtually always a
transudate
1. Pleural fluid protein/serum protein ratio greater than 0.5.
2. Pleural fluid LDH/serum LDH ratio greater than 0.6.
• Pleural fluid LDH greater than two thirds the upper limits
of normal of the serum LDH
19. Pleural Fluid
• Sources of benign conditions
– Primary pulmonary infection or infarction
– Secondary due to abdominal disease, i.e.
cirrhosis
• Sources of malignant conditions
– Most common sources are lung, breast,
lymphoid neoplasms, GI and mesothelioma
20. Pericardial Fluid
• Sources of benign conditions
– Congestive heart failure, infection,
radiation, hypothyroidism, uremia,
hypoproteinemia
• Sources of malignant conditions
– Commonly associated with lung or breast,
followed by lymphoma, sarcoma and
melanoma
21. Peritoneal Fluid
• Sources of benign conditions
– Portal venous hypertension,
hypoproteinemia and salt retention
• Sources of malignant conditions
– Commonly associated with ovary, breast,
GI, lymphoid neoplasms and mesothelioma
– In malignancies of unknown origin,
consider genital tract for women and GI
tract for men
22. COLLECTION
• Fluid is collected by needle aspiration (100
mL) from the respective cavities.
• Serous fluids – EDTA for cell counts and
morphology. For other tests in Heparin or
blood culture tubes.
• Fresh specimens for cytology may be stored
upto 48 hours in the refrigerator with
satisfactory results.
23. RECOMMENDED TESTS
ROUTINE
• Gross examination
• Pleural fluid/serum protein ratio
• Pleural fluid/serum LD ratio
• Examination of Romanowski-stained
smear(malignant cells, LE cells)
Useful tests in most patients
• Stains and cultures for microorganisms
• Cytology
24. Additional testing may aide in
diagnosis
• Glucose – Low in TB, rheumatoid disease and bacterial
infections
• Amylase – High in pancreatitis, esophageal perforation
• pH – Low in rheumatoid disease, hemothorax, acidosis
• Ammonia –Intestinal necrosis, perforation, effusion(-) vs.
urine(+)
• Creatinine – Negative in effusion, positive in urinothorax
• Bile – Included in the differential dx of green appearing
effusion
• Cell Block and Immunochemistry*– Tumor typing
25. • Electron Microscopy – Differentiate adenoca vs.
mesothelioma
• Flow Cytometry – Useful in hematopoietic malignancies.
• ADA - >40 U/L rapid evidence of tuberculous effusions.
• INF-Gamma – increased in tuberculous pleuritis.
• Lipids – chylous from pseudochylous.
• CRP – screening test for organ disease, parapneumonic
infections.
• TSA (Tuberculostearic acid) – Tuberculosis.
• Tumour markers – CEA, PSA, CA-125.
• Fibronectin – in malignant ascites.
26. SAAG
Diagnosis of
ascites due to
portal
hypertension is
established by
measurement of
serum ascites
albumin
gradient(SAAG).
29. MICROSCOPIC EXAMINATION
Cell counts :
• Total cell counts may be performed using
manual hemocytometer methods, however,
automated cell counts are increasingly used
with serous fluid specimens.
• Differential counts
30. N X Dilution factor
Area of total squares counted X Depth
Total cell count =
*Correlation of cell count with cytomorphological findings is essential.
Calculation of Cell count
31. CELL COUNT – PLEURAL FLUID
Total WBC count is almost never diagnostic
• >10,000/uL : Inflammation
• >50,000/uL : Parapneumonic effusions, usually
empyema.
• <5,000/uL : Chronic exudates(malignancy, TB)
• <1,000/uL : Transudates
35. Mesothelial cells
Bland cells forming a monolayer covering serous surfaces of body
cavities. (20 to 40 microns in diameter).
- Nuclei
• Single or binucleated
• Centrally located but can be eccentric
• Round to oval with well-defined, smooth nuclear borders
• Fine chromatin
• Inconspicuous nucleoli
– Cytoplasm
• Dense center with pale periphery
• Lacy “skirt” cell borders
• Blunt cytoplasmic processes due to degeneration
45. Normal Components
• Histiocytes
– Usually present in effusion. Prominent in cancer, TB and
embolism
• Lymphocytes
– Some amount usually present. Can be numerous in conditions
ranging from congestive heart failure and infections to carcinoma
and lymphoma
• Eosinophils
– Usually a good prognosis. Most eosinophilic effusions are pleural
and due to allergic reactions to dust. Other causes include
pulmonary infarct, pneumonia, trauma, hydatid disease
• Neutrophils
– Presence can have many causes, particularly infection. Malignant
effusions are seldom associated with acute inflammation
57. LE Cells
LE cell: Wright-stained smear of the pleural fluid shows a typical single LE cell
consisting of a neutrophil with flattened nucleus engulfing a central paler
homogenous mass.
60. Reactive changes
• Reactive changes are common and may be due
to:
– Pulmonary embolism or infarct
– Active cirrhosis or hepatitis
– Uremia
– Pancreatitis
– Long-term dialysis
– Radiation and chemotherapy
*usually accompanied with marked inflammation.
61. Reactive changes
• Features of reactive mesothelial cells include:
– Varying cell sizes
– Increased numbers of mesothelial cells
– Enlarged central or paracentral nuclei
– Binucleation or multinucleation
– Coarsening of chromatin that remains evenly
distributed
– Chromocenters and nucleoli may become prominent
– “Sibling images” are a clue
68. Malignant Mesothelioma
• Very rare, usually associated with asbestos
exposure
• Most cases occur in men aged 50 to 70
years, particularly with a background in
auto mechanics or construction
• Commonly found in the pleural cavity but
can occur in the peritoneal cavity as well
69. Malignant Mesothelioma
• Cytologic features:
– One cell population of malignant mesothelial cells
– Larger clusters with irregular, knobby, flower-like
borders
– Dense endoplasm with delicate, lacy ectoplasm
– Central enlarged nucleus with macronucleoli and
irregular borders
– Abnormal mitotic figures may be seen but are not
diagnostic of mesothelioma
75. Primary Effusion Lymphoma
• Very rare subtype of diffuse large B-cell
lymphoma
• Associated with human herpes virus 8 (HHV-
8)
• Pleural, pericardial or peritoneal effusion
• Most cases occur in HIV positive patients with
rare cases in immunocompromised patients
• Absence of mass lesion and HHV-8 positivity
is essential for diagnosis
76. Primary Effusion Lymphoma
• Population of single, large cells
• Nuclei range from round to irregular and
lobulated
• Coarse chromatin
• Prominent, irregular nucleoli
• Cytoplasm is scant to abundant
• Morphologically similar to diffuse large B-
cell lymphoma
80. Adenocarcinoma
• Cytologic features:
– Glandular acini, papillae or cell balls
– Increased N/C ratios
– Irregular nuclear membranes
– Abnormal chromatin
– Large or irregular nucleoli
– Secretory vacuoles with mucin
81. Specific Patterns of Adenocarcinoma
• Breast
– Cells are usually fairly bland and uniform
– Aggregates or predominantly single
– Diagnostic clues are cannonballs,
intracytoplasmic lumens and single file
chains of cells
– Positive for mucicarmine stain
85. Specific Patterns of Adenocarcinoma
• Lung
- Large pleomorphic cells that can range
from bland to bizarre
- Nuclei are often hyperchromatic with fine
to coarsely granular chromatin and
prominent nucleoli
- Cytoplasm is often vacuolated and may
contain mucin
89. Specific Patterns of Adenocarcinoma
• Ovarian
– 3 types
• Mucinous
• Serous
• Endometrioid
– Most often characterized by cells with large,
transparent vacuoles
– Presence of psammoma bodies may suggest
ovarian origin but not diagnostic of malignancy
93. Suggested Immunochemistry Markers
– Adenocarcinoma Ovary
Mucinous Adenocarcinoma
• CK 7 +
• CK 20 +
• BerEP4 +
• CA 125 +
Non-mucinous Adenocarcinoma
• CK 7 +
• CK 20 -
• ER/PR +
• CEA -
94. Gastric Carcinoma
• Cells with malignant features are present as
a distinct population. Some may exhibit
nuclear displacement by a large secretory
vacuole, a “signet ring” cell.
99. Suggested Immunochemistry Markers –
Squamous Carcinoma
• CK 5/6 +
• CEA +
• p63* +
* p63 staining is especially useful in
non-keratinizing SCC
100. Malignant Melanoma
• Cytologic features:
– Usually single, large cells
– Large, eccentric nuclei
– Frequent intranuclear cytoplasmic
invaginations
– Binucleation is common
– Very prominent nucleoli
– Melanin pigment presence is diagnostic
103. Small Cell Carcinoma
• Cytologic features:
- Tissue aggregates with molding
- Single file arrangements can be seen
- Small, rounded cells
- Coarse chromatin
- Inconspicuous nucleoli
106. Lymphoma/Leukemia
• Non-Hodgkin Lymphoma is most common and
accounts for 10-15% of malignant effusions
• In children, hematopoietic neoplasms are the
primary common cause of a malignant effusion
• Majority of patients will have biopsy proven
disease before effusion develops
• Reed-Sternberg cells in Hodgkin disease are
rarely found in effusions
107. Lymphoma/Leukemia
• Classification of the cells is possibly based on:
- Size of cells
- Degree of nuclear abnormalities (cleaved, non-cleaved)
- Resemblance of cells to lymphoblasts or Burkitt cells
• Cytologic features:
– Single cell, monomorphic cell pattern
– Small cells with scant, delicate cytoplasm
– High N/C ratios
– Irregular nuclear membranes (cleaves, nuclear knobs)
– Prominent nucleoli
113. References
1. Henry’s clinical diagnosis and management by laboratory
methods. In Joseph A, Knight MD, Carl R. Kjeldsberg MD,
editors. Cerebrospinal, synovial and serous body fluid.
Twenty first edition. Richard A. Mcpherson, Matthew R
Pincus.
2. Winifred Gray, Gabriella Kocjan, Diagnostic cytopathology. In
malcom Galloway, Maria Thorn, editors. Brain and
cerebrospinal fluid. Third Edition.
3. ThinPrep®
Non-Gyn Lecture Series. Body Fluid Cytology.
The patient is positioned sitting upright with arms raised and supported. A local anesthetic is applied and then the doctor inserts the needle into the pleural cavity and the sample is removed. Benign and malignant conditions can be diagnosed.
An intravenous (IV) line may be started and the person may be given medications prior to the sample collection. The patient is positioned lying down. A local anesthetic is applied, then the doctor inserts the needle into the space between the ribs (fifth to sixth intercostals space) on the left side of the chest and into the pericardial sac and removes a fluid sample. An ultrasound may be used to help guide the needle.
Sometimes medications will be introduced into the space during the pericardiocentesis, i.e. immunosuppressed patients with infection.
Peritoneal effusion is also known as ascites fluid. Causes range from cirrhosis to malignancies.
The patient is positioned lying down with the head of the bed raised. A local anesthetic is applied and then the doctor inserts the needle into the abdominal cavity and the sample is removed. A catheter may be used to drain larger fluid amounts or to drain recurrent accumulations.
Body cavities are made of two layers - the visceral layer covers the organs while the parietal layer lines the outer wall. Together they form a self-contained cavity that is lined with mesothelial cells called a serous cavity; specifically, the pleural cavity surrounding the lungs, the pericardial cavity surrounding the heart and the peritoneal cavity surrounding the internal organs of the abdomen.
Serous fluid is produced by the serous membranes (typically just a few milliliters) and acts as a lubricant for the organs.
High concentrations of lymphocytes and absence of mesothelial cells may indicate tuberculosis
Clear and non-clotted fluids tend to be benign while cloudy, bloody and/or clotted fluids tend to be malignant
Other causes for the formation of transudates include: nephrotic syndrome, myxedema, peritoneal dialysis, hypoproteinemia resulting from malnutrition, Meig’s syndrome, sarcoidosis and glomerulonephritis.
High cellularity can be due to an active inflammatory process affecting the body cavity. Other causes for the formation of exudates include: metastatic tumor, pulmonary infarction, autoimmune diseases, diseases of the GI tract, trauma, certain drugs, radiation therapy, post myocardial infarction, yellow nail syndrome (associated w/malignancy) sarcoidosis, uremia and idiopathic causes.
Most reliable method to differentiate transudates from exudates.
Infectious etiologies are most common in immunosuppressed patients.
Pericardial effusions may contain extremely reactive mesothelial cells.
C-reactive protein (CRP) is a glycoprotein produced by the liver, which is normally absent from the blood. The presence of acute inflammation with tissue destruction within the body stimulates its production. Therefore, a positive CRP indicates the presence of an inflammatory process.
>250 PMN ---- SBP
Color ; bloody---- trauma, malignancy, infarction.
Clot---- traumatic tap
HCT ---- serous fluid hematocrit simillar to peripheral blood suggestive of traumatic tap, lower is suggestive of hemorrhagic effusion. >50% of Peripheral blood
Ether test : fat solvent, to dissolve the lipid component.
Chylous effusion- obstruction of lymphatic duct---- trauma, tumour, TB, granuloma, lymphoma.
Specimen type: pleural fluid 20x
Sheets of benign mesothelial can contain upwards of 50 cells.
Specimen type: pleural fluid 40x
Higher magnification of the previous image.
Pericardial effusion: Pericardiocentesis may yield sheets of benign mesothelial cells similar to those found in other body cavity effusions. The etiology of pericardial effusions is more likely to be infectious (viral), autoimmune, inflammatory (myocardial infarction) or reactive (uremia). Tumor, especially lung, may also invade the pericardium.
Pericardial effusion 60x: Higher magnification of previous slide.
Specimen type: peritoneal wash 20x
Sometimes sheets fold so that overlapping of cells is evident. The benign nature of these mesothelial cells is obvious based on their uniform arrangement and appearance.
Peritoneal wash 40x
Benign mesothelial cells form a peritoneal wash can appear to be rounded up into a more 3D group with some overlap. Closely examine the uniform cells with benign features.
Pelvic wash: Benign mesothelial cells. Mesothelial cells can also have a cuboidal appearance with more condensed cytoplasm. Again, note the cohesive sheet of cells with uniformity of nuclei throughout.
Histiocytes have smaller nuclei than mesothelial cells with granular or vacuolated cytoplasm. Compare these histiocytes with the single mesothelial cell at the arrow.
Pleural fluid: Renal cell carcinoma. Note the dense cytoplasm.
Pleural fluid, 40x. Benign lymphocytes mixed in a proteinaceous background with benign mesothelial cells.
Eosinophils, binucleation and red cytoplasmic granules can be readily identified.
Ciliocytophthoria: detached ciliated tufts of fallopian tube origin. Relatively common in peritoneal specimens from females
Microorganisms: almost every type has been described in effusion
LE cells: suggestive of systemic lupus erythematosus but can be seen in rheumatoid arthritis and drug reactions as well as in multiple myeloma and Hodgkin’s disease. An LE cell is a neutrophil containing a hematoxylin body, which is a cytoplasmic inclusion of homogenized nuclear material. Look for them in unexplained pleural effusion in a woman of childbearing age.
Sickle cells: sickle-shaped RBC’s, can be seen in sickle cell anemia
Charcot-Leyden crystals: more likely to form with delayed processing and refrigeration of eosinophillic effusions
Psammoma bodies: not diagnostic of malignancy however, ovarian cancer is the most common malignancy with psammoma bodies in an effusion. Also found in benign conditions such as mesothelial hyperplasia and endosalpingiosis.
Collagen balls: cores of collagen usually covered with mesothelium. More common in peritoneal washes than in effusions. Can be seen in benign mesothelial proliferations and mesothelioma but are rare in adenocarcinoma
LE cell: Wright-stained smear of the pleural fluid shows a typical single LE cell consisting of a neutrophil with flattened nucleus engulfing a central paler homogenous mass.
Pelvic washing 40x: Psammoma body from a case of biopsy confirmed benign mesothelial hyperplasia with psammomatosis.
Concentric laminated calcified structures commonly seen in papillary ca of thyroid, papillary serous cyst adenocarcinoma ovary, papillary rcc, meningioma
Cholesterol and other types of crystals may be seen in peritoneal washes and fluids from other body sites. Cholesterol crystals typically appear as irregular birefringent plates, often with notched corners (Fig. 29-15). In chronic effusions (e.g., tuberculous
arthritis, RA, SLE),
Starch granules are indicative of glove powder contamination from a prior laparotomy or can be a contaminant from the gloves of the cytoprep tech.
Likely to contain marked inflammation, which is not usually associated with carcinoma. Be cautious when diagnosing malignancy in patients with conditions known to induce marked reactive changes.
Mesothelial cells in pericardial fluid tend to be highly reactive. Although reactive atypia can be severe, it affects the cells more or less uniformly, resulting in the “sibling image” characteristic of benign cells. In contrast, a secondary “foreign” population of cells usually indicates metastasis.
Pleural effusion 6ox: Reactive mesothelial cells can have a wide range of sizes.
Pleural effusion 60x: Enlarged nuclei, small multiple nucleoli and spaces “windows” between adjacent cells. Inflammatory cells are present in the background.
Pleural fluid 60x: Reactive mesothelial cells can exhibit coarse chromatin, irregular nuclear outlines and nucleoli. It is important to look for a spectrum of changes and to correlate the cytology with clinical history. Notice the “windows”.
Pleural fluid 60x: Reactive mesothelial cells tend to present in a more monolayer arrangement and not in the large 3-dimensional clusters of malignant mesothelioma. Again notice the “windows”.
Desmin, p53 and EMA can be useful in distinguishing benign from malignant mesothelial cells but this can be variable.
Most commonly located on the right side of the pleural cavity. Heavy and prolonged exposure to asbestos can also lead to peritoneal mesothelioma.
Clue to diagnose mesothelioma is “more and bigger cells in more and bigger clusters”.
Cell clusters in adenocarcinoma have smooth community borders, with eccentric nuclei and delicate pale to foamy cytoplasm
Final determination may require cell block with immunohistochemistry or even electron microscopy.
.
Pleural effusion (Mesothelioma) – Higher magnification of the previous image.
Pleural effusion - Tumor cells may be seen in a background of blood and proteinaceous debris. Numerous large clusters of cells may a feature of malignancy.
Pleural Fluid – Abnormal mitotic figures may be noted but can also be associated with other malignancies, as well as reactive mesothelial cells.
Electron microscopy may also be needed to differentiate difficult cases.
Pleural fluid 20x. PEL cells are obviously abnormal even at low power.
Pleural fluid 40x. Cells from this tumor range from immunoblastic (round nucleus with a prominent nucleolus) to anaplastic (large, irregular, multilobulated).
When associated with HIV and HHV-8 infection, these lymphomas are negative for typical B-cell as well as carcinoma and melanoma markers.
Most common cause of malignant effusions.
Breast cancer is the most common cause of malignant pleural effusion in women.
Peritoneal effusion (Breast ca) – Many small clusters and single malignant cells contrast with benign mesothelial cells. As in pleural effusions, these cells tend to be present in large rounded clusters as well as singly.
Peritoneal effusion (breast ca) – Note the large intracytoplasmic vacuoles with mucin droplets
Metastatic lung carcinoma is the most common causes of malignant pleural effusions in men and the second most common cause in women.
Pleural effusion (Lung ca) – Often it is easy to distinguish adenocarcinoma from mesothelioma. Note the eccentric nuclei, lacy cytoplasm and community borders. However, electron microscopy and immunohistochemistry may sometimes be necessary to assist in defining a primary site. Knowing the patient’s history is always the key to identifying metastases.
Pleural effusion (Moderately differentiated lung ca) – Papillary glandular arrangements of tumor cells, prominent nucleoli, vacuolization and mitotic figures.
Ovarian cancer is the most common cause of malignant ascites. Differential diagnoses include non-small cell lung cancer, pancreatic carcinoma and mesothelioma. Mucinous type resembles endocervical cells or GI malignancy. Serous type resembles fallopian tubes. Endometrioid type is identical to endometrial carcinoma.
Pleural effusion - Cells of papillary serous ovarian adenocarcinoma in a pleural effusion. Their cell and nuclear size is variable. Increased nuclear to cytoplasmic ratio and cytoplasmic vacuoles are features. Cells may exist singly or in small acinar groups.
Peritoneal effusion - Papillary cluster of glandular serous borderline tumor forming rounded “cannon-balls” of tumor cells. Note the smooth border, compared to the scalloped border of reactive mesothelial cells.
Peritoneal wash (Ovarian serous borderline tumor) - Papillary cluster of tumor cells with prominent cytoplasmic vacuolization. Washes are an integral part of staging laparoscopy. Because of the washing procedure, tumor cells generally come off in three- dimensional cohesive groups and may be admixed with sheets of benign mesothelium. The tumor cells are easily distinguished by size, malignant characteristics and crowded configurations.
Peritoneal effusion (gastric adenoca) – Cells with malignant features are present as a distinct population. Some may exhibit nuclear displacement by a large secretory vacuole, a “signet ring” cell.
Adenoca of the stomach shows variable immunochemistry staining patterns.
Primary sites are commonly lung, larynx and female genital tract. Common type of cancer but rarely sheds diagnostic cells into effusions.
Pleural fluid - Characteristic features of squamous cell carcinoma are seen: orangeophilic cytoplasm and hyperchromatic nuclei
Effusion fluid may be dark brown or black. Metastatic melanoma is notorious for its ability to mimic a wide variety of other neoplasms, as well as for late recurrences.
Peritoneal effusion (Malignant melanoma) – May present in effusions with or without an antecedent skin tumor. They often metastasize to unusual places such as small bowel serosa.
Differential diagnoses include breast cancer (small cells, single file chains of cells; look for mucin secretion) and small blue cell tumors of childhood (small cell carcinoma is a tumor of older adult smokers).
Pleural effusion – Small dark cells of small cell undifferentiated carcinoma can appear singly and in small groups. Note the nuclear molding.
Cytomorphologic features such as cell size and nuclear characteristics (round, irregular, cleaved as well as chromatin pattern and nucleoli) are important in categorizing the lymphoid population. Flow cytometry and immunohistochemistry may be necessary to diagnose lymphoma or leukemia in a patient with no prior clinical history.
Pleural effusion (Non-Hodgkin’s lymphoma) - These neoplastic lymphocytes appear small and monotonous, but compared to the background lymphocytes, they are considerably larger. Nuclei are vesicular with nuclear clefting and lobation and variably prominent nucleoli.
Pleural effusion (Non-Hodgkin’s lymphoma) – High power of previous image.
Reed-Sternberg cells are much larger than normal cells. Reed Sternberg cells ----- binucleated giant cell with prominent inclusion-like nucleoli.
Pleural effusion (Chronic lymphocytic leukemia) - An example of small, round lymphocytes in a pleural effusion. In the absence of clinical history, the differential diagnosis includes inflammatory conditions such as tuberculosis, autoimmune diseases and lymphoproliferative disorders.
Immunochemistry, flow cytometry and molecular studies may all need to be performed to accurately diagnose benign proliferations and various small lymphocytic lymphomas.