Difference between revisions of "Mesothelial cytopathology"

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[[Image:Benign mesothelial cells - pleural fluid -- high mag.jpg|thumb|right|300px|Benign mesothelial cells from a pleural fluid specimen. (WC)]]
[[Image:Lung_adenocarcinoma_-_pleural_fluid_--_very_high_mag.jpg|thumb|right|300px|Adenocarcinoma (lung) and benign mesothelial cells in a pleural fluid specimen. (WC)]]
'''Mesothelial cytopathology''' is a large part of cytopathology.  The article deals with cytopathology specimens from spaces lined with mesothelium, i.e. it deals with pericardial fluid, peritoneal fluid and pleural fluid.
'''Mesothelial cytopathology''' is a large part of cytopathology.  The article deals with cytopathology specimens from spaces lined with mesothelium, i.e. it deals with pericardial fluid, peritoneal fluid and pleural fluid.


An introduction to cytopathology is in the ''[[cytopathology]]'' article.   
An introduction to cytopathology is in the ''[[cytopathology]]'' article.   


=Specimen types=
A general [[differential diagnosis]] of pleural effusion is given in the ''[[pleural effusion]]'' article.
 
''Pleural fluid'', ''pleural cytopathology'', ''peritoneal fluid'', and ''peritoneal cytopathology'' redirect to here.
 
=Overview=
*[[Sensitivity]] moderate for malignancy (60%).<ref name=pmid>{{Cite journal  | last1 = Karoo | first1 = RO. | last2 = Lloyd | first2 = TD. | last3 = Garcea | first3 = G. | last4 = Redway | first4 = HD. | last5 = Robertson | first5 = GS. | title = How valuable is ascitic cytology in the detection and management of malignancy? | journal = Postgrad Med J | volume = 79 | issue = 931 | pages = 292-4 | month = May | year = 2003 | doi =  | PMID = 12782778 }}</ref>
 
===Specimen types===
*'''Wash''', e.g. ''peritoneal wash'': expect sheets of (benign squamous) cells.
*'''Wash''', e.g. ''peritoneal wash'': expect sheets of (benign squamous) cells.
*'''Spontaneous''', e.g. ''pleural fluid'': usually no large sheets.
*'''Spontaneous''', e.g. ''pleural fluid'': usually no large sheets.


Note:
Note:
This distinction is important as ''wash'' specimens may have pseudopapillae.  
This distinction is important as ''wash'' specimens may have pseudopapillae.


=Approach=
===Approach===
Look for:
Look for:
#Two cell populations.
#Two cell populations.
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#Small cells with high [[NC ratio]].
#Small cells with high [[NC ratio]].


 
===Features of malignancy===
==Malignancy==
Strongly suggestive of malignancy:
Strongly suggestive of malignancy:
*3-D clusters.
*3-D clusters.
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*High NC ratio.
*High NC ratio.


=Main DDx=
===Differential diagnosis===
*[[Adenocarcinoma]] not otherwise specified (NOS) - most common.
*Reactive mesothelium.
*Reactive mesothelium.
*Malignant mesothelioma.
*Malignant mesothelioma.
*[[Adenocarcinoma]] not otherwise specified (NOS).
*[[Serous carcinoma]].
*[[Serous carcinoma]].
*[[Lymphoma]].
*[[Lymphoma]].
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*[[Endosalpingiosis]].
*[[Endosalpingiosis]].
*[[Endometriosis]].
*[[Endometriosis]].
*[[Small cell carcinoma]].


===Peritoneal cavity specific===
====Peritoneal cavity specific====
*[[HCC]] may be assoc. with ascites... but it is rarely positive for malignant cells.<ref name=Ref_APBR679>{{Ref APBR|679}}</ref>
*[[Hepatocellular carcinoma]] (HCC) may be associated with ascites... but it is rarely positive for malignant cells.<ref name=Ref_APBR679>{{Ref APBR|679}}</ref>
**HCC in ascites fluid is super rare -- ''I haven't seen a case''.<ref>SB. 8 January 2010.</ref>
**HCC in ascites fluid is super rare -- ''I haven't seen a case''.<ref>SB. 8 January 2010.</ref>


=Normal mesothelium=
=Normal mesothelium=
===General===
Often seen in the context of:
*Gynecologic surgeries - done to exclude malignancy.
*Taps for ascites.
===Cytology===
Features:<ref name=Ref_APBR674>{{Ref APBR|674}}</ref>
Features:<ref name=Ref_APBR674>{{Ref APBR|674}}</ref>
*"Window" or "space" between attached cells (due to microvilli).
*"Window" or "space" between attached cells (due to microvilli).
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*Nucleoli (in reactive cells).
*Nucleoli (in reactive cells).


Images:
Note - abnormal features:
*[http://commons.wikimedia.org/wiki/File:Mesothelium_peritoneal_wash_intermed_mag.jpg Peritoneal wash - benign mesothelial cells in sheets (WC)].
*Large clusters of cells, e.g. 150+ micrometres.
*[http://commons.wikimedia.org/wiki/File:Mesothelium_peritoneal_wash_high_mag.jpg Peritoneal wash - benign mesothelial cells in sheets - high mag. (WC)].
 
===Images===
<gallery>
Image:Mesothelium_peritoneal_wash_intermed_mag.jpg | Peritoneal wash - benign mesothelial cells in sheets (WC)
Image:Mesothelium_peritoneal_wash_high_mag.jpg | Peritoneal wash - benign mesothelial cells in sheets - high mag. (WC)
Image:Benign mesothelial cells - pleural fluid -- high mag.jpg | Pairs of mesothelial cells with an intercellular window. (WC)
</gallery>
 
=Reactive mesothelium=
===General===
*May be due to any number of causes.
*Can be severe in the context of [[chronic renal failure|(peritoneal) dialysis]].<ref name=pmid2323293>{{Cite journal  | last1 = Selvaggi | first1 = SM. | last2 = Migdal | first2 = S. | title = Cytologic features of atypical mesothelial cells in peritoneal dialysis fluid. | journal = Diagn Cytopathol | volume = 6 | issue = 1 | pages = 22-6 | month =  | year = 1990 | doi =  | PMID = 2323293 }}</ref>
 
===Cytology===
:''See [[Mesothelial_cytopathology#Malignant_mesothelioma|mesothelioma]]''.
 
====Images====
<gallery>
Image: Peritoneal fluid - post-DC insertion -- high mag.jpg | PF - high mag. (WC)
Image: Peritoneal fluid - post-DC insertion -- very high mag.jpg | PF - very high mag. (WC)
Image: Peritoneal fluid - post-DC insertion - alt -- very high mag.jpg | PF - very high mag. (WC)
</gallery>
===Sign out===
<pre>
Pleural Fluid, Right, Thoracentesis:
- Negative for malignant cells.
- Reactive mesothelial cells present in a background of abundant lymphocytes.  


Abnormal features:
Comment:  
*Large clusters of cells, e.g. 150+ micrometres.
Additional sampling should be considered within the clinical context.  
</pre>


=Specific diagnoses - benign=
=Specific diagnoses - benign=
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This has a large DDx:
This has a large DDx:
*Trauma with air in the pleural cavity.
*Trauma with air in the pleural cavity.
**Repeated tap in the context of pneumothorax.
**Repeated tap in the context of [[pneumothorax]].
*[[Pulmonary infarct]].
*[[Pulmonary infarct]].
*[[Pneumonia]].
*[[Pneumonia]].
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===Cytology===
===Cytology===
Features:
Features:
*Lupus erythematosus cells, usually abbreviated ''LE cells'':<ref>URL:[http://www.tabers.com/tabersonline/ub/view/Tabers/143167/34/L_E__cell http://www.tabers.com/tabersonline/ub/view/Tabers/143167/34/L_E__cell]. Accessed on: 12 April 2012.</ref>
*Lupus erythematosus cells, usually abbreviated ''[[LE cell]]s'':<ref>URL:[http://www.tabers.com/tabersonline/ub/view/Tabers/143167/34/L_E__cell http://www.tabers.com/tabersonline/ub/view/Tabers/143167/34/L_E__cell]. Accessed on: 12 April 2012.</ref>
**Pink blobs (representing a denatured nuclei) - phagocytosed by macrophages or [[PMN]]s.<ref>URL: [http://library.med.utah.edu/WebPath/IMMHTML/IMM008.html http://library.med.utah.edu/WebPath/IMMHTML/IMM008.html]. Accessed on: 12 April 2012.</ref>
**Pink blobs (representing a denatured nuclei) - phagocytosed by a [[neutrophil]].<ref>URL: [http://library.med.utah.edu/WebPath/IMMHTML/IMM008.html http://library.med.utah.edu/WebPath/IMMHTML/IMM008.html]. Accessed on: 12 April 2012.</ref>


Image:  
Image:  
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Notes:
Notes:
*Single cells/small clusters - suggestive of mesothelioma vs. serous carcinoma. (???)
*Single cells/small clusters - suggestive of mesothelioma vs. serous carcinoma. (???)
Images:
*[http://www.acta-cytol.com/feature/2006/feature062006.php IHC mesothelioma (acta-cytol.com)].
*[http://www.nature.com/modpathol/journal/v17/n4/fig_tab/3800067f2.html IHC mesothelioma (nature.com)].
*[http://commons.wikimedia.org/wiki/File:Mesothelioma_cytology_1.jpg Mesothelioma - 1 (WC)].
*[http://commons.wikimedia.org/wiki/File:Mesothelioma_cytology_2.jpg Mesothelioma - 2 (WC)].


Mesothelioma versus reactive mesothelium:<ref name=Ref_DCHH359-60>{{Ref DCHH|359-60}}</ref>
Mesothelioma versus reactive mesothelium:<ref name=Ref_DCHH359-60>{{Ref DCHH|359-60}}</ref>
{| class="wikitable"
{| class="wikitable sortable"
|-
|-
!
! Characteristic
! Reactive mesothelial cells
! Reactive mesothelial cells
! Mesothelioma
! Mesothelioma
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Note 1:
Note 1:
*Best assessed on single cells.
*Best assessed on single cells.
====Images====
www:
*[http://www.acta-cytol.com/feature/2006/feature062006.php IHC mesothelioma (acta-cytol.com)].
*[http://www.nature.com/modpathol/journal/v17/n4/fig_tab/3800067f2.html IHC mesothelioma (nature.com)].
<gallery>
Image:Mesothelioma_cytology_1.jpg | Mesothelioma - 1 (WC)
Image:Mesothelioma_cytology_2.jpg | Mesothelioma - 2 (WC)
</gallery>


===IHC===
===IHC===
*Calretin +ve.
*[[Calretinin]] +ve.
*WT-1 +ve.
*WT-1 +ve.
*D2-40 +ve.
*[[D2-40]] +ve.
*TTF-1 -ve.
*[[TTF-1]] -ve.
*CEA -ve.
*CEA -ve.
*[[p63]] -ve.<ref name=pmid18064689>{{Cite journal  | last1 = Pu | first1 = RT. | last2 = Pang | first2 = Y. | last3 = Michael | first3 = CW. | title = Utility of WT-1, p63, MOC31, mesothelin, and cytokeratin (K903 and CK5/6) immunostains in differentiating adenocarcinoma, squamous cell carcinoma, and malignant mesothelioma in effusions. | journal = Diagn Cytopathol | volume = 36 | issue = 1 | pages = 20-5 | month = Jan | year = 2008 | doi = 10.1002/dc.20747 | PMID = 18064689 }}</ref>
==Adenocarcinoma==
===General===
*[[Diagnosis]] represent a large number of distinct entities - see ''[[adenocarcinoma NOS]]''.


==Breast carcinoma in fluid==
===Cytology===
===Cytology===
Breast adenocarcinoma in fluid - features:<ref name=Ref_APBR675>{{Ref APBR|675}}</ref>
Adenocarcinoma in fluid - features:<ref name=Ref_APBR675>{{Ref APBR|675}}</ref>
*Classically large morules (clusters of cells that are heaped/are "3-dimensional"), known as ''cannonballs'', with "community borders".
*Classically large morules (clusters of cells that are heaped/are "3-dimensional"), known as ''cannonballs'', with "community borders".
**"Community border" = smooth, low surface area border; should be differentiated from a "knobby" border seen in mesothelioma.
**"Community border" = smooth, low surface area border; should be differentiated from a "knobby" border seen in mesothelioma.
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*Lung.
*Lung.
*GI.
*GI.
====Images====
=====Case 1=====
<gallery>
Image: Adenocarcinoma - pleural fluid  -- high mag.jpg | Adenocarcinoma - high mag. (WC)
Image: Adenocarcinoma - pleural fluid  -- very high mag.jpg | Adenocarcinoma - very high mag. (WC)
</gallery>
<gallery>
Image: Lung adenocarcinoma - pleural fluid -- high mag.jpg | Lung adenocarcinoma - high mag. (WC)
Image: Lung adenocarcinoma - pleural fluid -- very high mag.jpg | Lung adenocarcinoma - very high mag. (WC)
Image: Lung adenocarcinoma - pleural fluid - 2 -- high mag.jpg | Lung adenocarcinoma - high mag. (WC)
Image: Lung adenocarcinoma - pleural fluid - 2 -- very high mag.jpg | Lung adenocarcinoma - very high mag. (WC)
</gallery>
=====Case 2=====
<gallery>
Image: Adenocarcinoma - pleural fluid 3 -- high mag.jpg | Adenocarcinoma - high mag. (WC)
Image: Adenocarcinoma - pleural fluid 3 -- very high mag.jpg | Adenocarcinoma - very high mag. (WC)
Image: Adenocarcinoma - pleural fluid 3 - alt -- very high mag.jpg | Adenocarcinoma - very high mag. (WC)
Image: Adenocarcinoma - pleural fluid 3 - TTF-1 -- high mag.jpg | Adenocarcinoma - TTF-1 - high mag. (WC)
Image: Adenocarcinoma - pleural fluid 3 - TTF-1 -- very high mag.jpg | Adenocarcinoma - TTF-1 - very high mag. (WC)
</gallery>
===IHC===
Breast:
*ER +ve/-ve.
*Calretinin -ve.
Colon:
*CK20 +ve.
*CDX2 +ve.
*Calretinin -ve.
Lung:
*TTF-1 +ve.
*Calretinin -ve.


==Colorectal adenocarcinoma==
==Colorectal adenocarcinoma==
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**Pseudostratified cells.
**Pseudostratified cells.
**Columnar cells.
**Columnar cells.
Note:
*See ''adenocarcinoma'' section above for other types of adenocarcinoma.


==Serous carcinoma==
==Serous carcinoma==
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**Large clusters of cells / micropapillae (?).
**Large clusters of cells / micropapillae (?).
**Nuclear overlap.
**Nuclear overlap.
**+/-True papillae.<ref>SB. 12 January 2010.</ref>
**+/-True papillae.<ref name=scott>Boerner, S. 12 January 2010.</ref>
 
Images:
*[http://pathy.med.nagoya-u.ac.jp/atlas/misc/serous.html Ascites fluid serous adenocarcinoma (nagoya-u.ac.jp)].
*[http://commons.wikimedia.org/wiki/File:Serous_carcinoma_cytology.jpg Serous carcinoma - cytology - low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Uterine_serous_carcinoma_high_mag.jpg Serous carcinoma - histology - high mag. (WC)].


Note 1 - classic features of serous (see ''[[gynecologic pathology]]'' article):
Note 1 - classic features of serous (see ''[[gynecologic pathology]]'' article):
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*Cervix.
*Cervix.
*[[Serous endometrial carcinoma|Endometrium]].
*[[Serous endometrial carcinoma|Endometrium]].
**Intravacuolar neutrophils are erroneously believed to be indicative of this.<ref>SB. 12 January 2010.</ref>
**Intravacuolar neutrophils are erroneously believed to be indicative of this.<ref name=scott>Boerner, S. 12 January 2010.</ref>
*Uterine tube.
*Uterine tube.
*[[Ovarian serous carcinoma|Ovary]].
*[[Ovarian serous carcinoma|Ovary]].
*Primary peritoneal.
*Primary peritoneal.
====Images====
www:
*[http://pathy.med.nagoya-u.ac.jp/atlas/misc/serous.html Ascites fluid serous adenocarcinoma (nagoya-u.ac.jp)].
<gallery>
Image:Serous_carcinoma_cytology.jpg | Serous carcinoma - cytology - low mag. (WC)
Image:Uterine_serous_carcinoma_high_mag.jpg | Serous carcinoma - histology - high mag. (WC)
</gallery>


===IHC===
===IHC===
*WT-1 +ve.
*WT-1 +ve.
*CA-125 +ve.
*[[CA-125]] +ve.
*D2-40 +ve.
*D2-40 +ve.
==Lymphoma==
===General===
*Can only be reasonably certain for ''large cell lymphomas'', e.g. ''[[DLBCL]]''.
**The diagnosis of [[small cell lymphomas]] relies on architecture and immunostains.
===Cytology===
Features:
*Dyscohesive cells ~2x a resting lymphocyte - usually with scant blue cytoplasm.
DDx:
*[[Small cell carcinoma]].
*Other [[small round cell tumours]].
====Images====
<gallery>
Image: Lymphoma - pleural fluid -- intermed mag.jpg | Lymphoma - intermed. mag.
Image: Lymphoma - pleural fluid - alt -- high mag.jpg | Lymphoma - high mag.
Image: Lymphoma - pleural fluid - alt -- very high mag.jpg | Lymphoma - very high mag.
Image: Lymphoma - pleural fluid - DQ -- high mag.jpg | Lymphoma - high mag.
Image: Lymphoma - pleural fluid - DQ -- very high mag.jpg | Lymphoma - very high mag.
</gallery>


=See also=
=See also=
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