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Mesothelial cytopathology (view source)

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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.   


==Cavity fluids==
A general [[differential diagnosis]] of pleural effusion is given in the ''[[pleural effusion]]'' article.
===Basic types===
 
''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.


===Main DDx===
Note:
*Mesothelium.
This distinction is important as ''wash'' specimens may have pseudopapillae.
*Other.
**Adenocarcinoma not otherwise specified (NOS).
**[[Serous carcinoma]].
**[[Squamous carcinoma]].
**Lymphoma.


===Peritoneal cavity specific===
===Approach===
*HCC may be assoc. with ascites... but it is rarely positive for malignant cells.<ref name=Ref_APBR679>{{Ref APBR|679}}</ref>
Look for:
**HCC in ascites fluid is super rare -- ''I haven't seen a case''.<ref>SB. 8 January 2010.</ref>
#Two cell populations.
#Large dark objects.
#Boerner's red flags.
 
Boerner's red flags:
#3-D clusters.
#*Doublet & triplets common.
#*Quads-to-Quints - sweat breaks-out.
#*Sextuplets... very nervous.
#"Busy" slide:
#*Nuclear pleomorphism.
#*Too many "intermediate cells".
#*Mitoses - 1-2/slide is "many".
#Vacuolated cytoplasm.
#Small cells with high [[NC ratio]].


===Malignancy===
===Features of 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.


==Normal mesothelium==
===Differential diagnosis===
*[[Adenocarcinoma]] not otherwise specified (NOS) - most common.
*Reactive mesothelium.
*Malignant mesothelioma.
*[[Serous carcinoma]].
*[[Lymphoma]].
 
Less common:
*[[Squamous carcinoma]].
*[[Rheumatoid pleuritis]].
*[[Systemic lupus erythematosus pleurisy]].
*[[Endosalpingiosis]].
*[[Endometriosis]].
*[[Small cell carcinoma]].
 
====Peritoneal cavity specific====
*[[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>
 
=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.
 
Comment:
Additional sampling should be considered within the clinical context.
</pre>


Abnormal features:
=Specific diagnoses - benign=
*Large clusters of cells, e.g. 150+ micrometres.
==Eosinophilic pleuritis==
===General===
This has a large DDx:
*Trauma with air in the pleural cavity.
**Repeated tap in the context of [[pneumothorax]].
*[[Pulmonary infarct]].
*[[Pneumonia]].
*Parasitic infections.
*[[Hodgkin lymphoma]].
*Idiopathic - most common cause.
 
===Cytology===
Features:
*Eosinophils >10%.
 
==Rheumatoid pleuritis==
===General===
*History of [[rheumatoid arthritis]].
*Cytologic appearance considered to be ''pathognomonic''.<ref name=pmid2197838/>
 
===Cytology===
Features:<ref name=pmid2197838>{{Cite journal  | last1 = Naylor | first1 = B. | title = The pathognomonic cytologic picture of rheumatoid pleuritis. The 1989 Maurice Goldblatt Cytology award lecture. | journal = Acta Cytol | volume = 34 | issue = 4 | pages = 465-73 | month =  | year =  | doi =  | PMID = 2197838 }}</ref>
*Large (single) multinucleated cells - classically spindled.
**May have epithelioid morphology.
*Necrotic debris - fluffy orange-to-blue crap.
 
Note:
*Necrotizing granulomatous inflammation.
 
==Systemic lupus erythematosus pleurisy==
{{Main|Systemic lupus erythematosus}}
*[[AKA]] ''systemic lupus erythematosus pleuritis''.
===General===
*Not common.
*Distinctive cytology.
 
===Cytology===
Features:
*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 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:
*[http://library.med.utah.edu/WebPath/IMMHTML/IMM008.html LE cell (utah.edu)].
*[http://www.tabers.com/tabersonline/ub/view/Tabers/143167/34/L_E__cell LE cell (tabers.com)].


==Mesothelioma==
=Specific diagnoses - malignant=
==Malignant mesothelioma==
{{Main|Malignant mesothelioma}}
===General===
===General===
*Can be challenging to diagnose.
*Can be challenging to diagnose.
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#*Multiple nucleoli.
#*Multiple nucleoli.
#*Irregular nucleoli (strong).
#*Irregular nucleoli (strong).
Image:
*[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)].


Notes:
Notes:
*Single cells/small clusters - suggestive of mesothelioma vs. serous carcinoma. (???)
*Single cells/small clusters - suggestive of mesothelioma vs. serous carcinoma. (???)


===IHC===
Mesothelioma versus reactive mesothelium:<ref name=Ref_DCHH359-60>{{Ref DCHH|359-60}}</ref>
*Calretin.
{| class="wikitable sortable"
 
==Mesothelial fluid cytopathology tables==
===Mesothelioma vs. reactive mesothelium<ref name=Ref_DCHH359-60>{{Ref DCHH|359-60}}</ref>===
{| class="wikitable"
|-
|-
!
! Characteristic
! Reactive mesothelial cells
! Reactive mesothelial cells
! Mesothelioma
! Mesothelioma
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*Best assessed on single cells.
*Best assessed on single cells.


==Breast carcinoma in fluid==
====Images====
Breast adenocarcinoma in fluid - features:<ref name=Ref_APBR675>{{Ref APBR|675}}</ref>
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===
*[[Calretinin]] +ve.
*WT-1 +ve.
*[[D2-40]] +ve.
*[[TTF-1]] -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]]''.
 
===Cytology===
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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*GI.
*GI.


==Colorectal adenocarcinoma (CRA)==
====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==
{{Main|Colorectal adenocarcinoma}}
*May be abbreviated ''CRA''.
===General===
*Cytology may be distinctive.
 
===Cytology===
Features:
Features:
*Cannonballs (non-specific).
*Cannonballs (non-specific).
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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==
General:
{{Main|Serous carcinoma}}
*SB believes one can and ought to separate ''adenocarcinoma'' from ''serous carcinoma''.
===General===
*S. Boerner believes one can and ought to separate ''adenocarcinoma'' from ''serous carcinoma''.


===Microscopic===
Features:
Features:
*Large nucleoli.<ref name=pmid2916358>{{Cite journal  | last1 = Kuebler | first1 = DL. | last2 = Nikrui | first2 = N. | last3 = Bell | first3 = DA. | title = Cytologic features of endometrial papillary serous carcinoma. | journal = Acta Cytol | volume = 33 | issue = 1 | pages = 120-6 | month =  | year =  | doi =  | PMID = 2916358 }}</ref>
*Large nucleoli.<ref name=pmid2916358>{{Cite journal  | last1 = Kuebler | first1 = DL. | last2 = Nikrui | first2 = N. | last3 = Bell | first3 = DA. | title = Cytologic features of endometrial papillary serous carcinoma. | journal = Acta Cytol | volume = 33 | issue = 1 | pages = 120-6 | month =  | year =  | doi =  | PMID = 2916358 }}</ref>
Line 140: Line 317:
**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)].


Note 1 - classic features of serous (see ''[[gynecologic pathology]]'' article):
Note 1 - classic features of serous (see ''[[gynecologic pathology]]'' article):
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*Cilia.
*Cilia.
*Papillae.
*Papillae.
*Psammoma bodies.
*[[Psammoma bodies]].


DDx of serous carcinoma (found in ascites fluid):
DDx of [[serous carcinoma]] (found in ascites fluid):
*Cervix.
*Cervix.
*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.
*Ovary.
*[[Ovarian serous carcinoma|Ovary]].
*Primary peritoneal.
*Primary peritoneal.


IHC:
====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===
*WT-1 +ve.
*WT-1 +ve.
*CA-125 +ve.
*[[CA-125]] +ve.
*D2-40 +ve.
*D2-40 +ve.


==See also==
==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=
*[[Cytopathology]].
*[[Cytopathology]].
*[[Urine cytopathology]].
*[[Urine cytopathology]].
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*[[Urothelium]].
*[[Urothelium]].


==References==
=References=
{{reflist|2}}
{{reflist|2}}


==External links==
=External links=
*[http://www.histopathology-india.net/MesoCyto.htm Mesothelioma (histopathology-india.net)].
*[http://www.histopathology-india.net/MesoCyto.htm Mesothelioma (histopathology-india.net)].
*[http://www.cytology-asc.com/cec/respiratory/respneopl.htm Respiratory cytopathology (Australian Society)].
*[http://www.cytology-asc.com/cec/respiratory/respneopl.htm Respiratory cytopathology (Australian Society)].


[[Category:Cytopathology]]
[[Category:Cytopathology]]
Michael
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