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==Pathology simplified==
==Pathology simplified==
===Blue & pink===
H&E is the standard...
H&E is the standard...
*Too much '''PINK''' = DEAD ([[necrosis]]).
*Too much '''PINK''' = DEAD ([[necrosis]]).
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In words:
In words:
*''Blue is bad and pink is dead!''<ref>Often said by STC.</ref>
*''Blue is bad and pink is dead!''<ref>Streutker, C. 8 June 2013.</ref>


Note:
Note:
*Lymph nodes are very blue... they aren't necessarily bad.
*There is a lengthy list of things that are blue and ''not'' "bad"... that why a pathology residency is years.
**[[Lymph node]]s are very blue... they aren't necessarily bad.
**Reactive processes can be very blue... they aren't bad.
 
===Three questions===
Pathology can be boiled down to:
#What is it?
#*Biopsies.
#Did I get it all?
#*Resections.
#Did I get the right thing?
#*Most other things.


==Terms==
==Terms==
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*''Argyrophilic'' means has an affinity for silver<ref>URL: [http://www.merriam-webster.com/medical/argyrophilic http://www.merriam-webster.com/medical/argyrophilic]. Accessed on: 29 August 2011.</ref><ref>URL: [http://en.wiktionary.org/wiki/argyrophilic http://en.wiktionary.org/wiki/argyrophilic]. Accessed on: 29 August 2011.</ref>/loves silver/stains with silver.
*''Argyrophilic'' means has an affinity for silver<ref>URL: [http://www.merriam-webster.com/medical/argyrophilic http://www.merriam-webster.com/medical/argyrophilic]. Accessed on: 29 August 2011.</ref><ref>URL: [http://en.wiktionary.org/wiki/argyrophilic http://en.wiktionary.org/wiki/argyrophilic]. Accessed on: 29 August 2011.</ref>/loves silver/stains with silver.
===Morphologic patterns===
===Morphologic patterns===
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
{{Main|Morphologic patterns}}
! Name of pattern
This covers things like ''cribriform'', ''hobnail'', ''herring bone'' and many others.
! Meaning
! DDx (incomplete/abbrev. list)
! Image
|-
| Hobnail
| basement membrane area < area exposed to luminal surface
| [[angiosarcoma]], clear cell carcinoma
| [[Image:Epithelioid_angiosarcoma_-_very_high_mag.jpg |thumb|center|150px| [[Angiosarcoma]] - very high mag. (WC/Nephron)]]
|-
| Storiform
| spiral appearance ''or'' cartwhell pattern<ref>Storiform. dictionary.com. URL: [http://dictionary.reference.com/browse/storiform http://dictionary.reference.com/browse/storiform]. Accessed on: April 24, 2009.</ref>
| [[solitary fibrous tumour]], [[DFSP]], [[dermatofibroma]], [[UPS]]
| [[Image:Storiform_pattern_-_very_high_mag.jpg | thumb| center|150px| [[DFSP]] - very high mag. (WC/Nephron)]]
|-
| Fascicular
| the long axis of the (spindle) cells are perpendicular to one another in adjacent bundles of cells
| [[leiomyoma]], [[leiomyosarcoma]]
| [[Image:Cutaneous_leiomyosarcoma_-_very_high_mag.jpg| thumb | center | 150px | [[Leiomyosarcoma]] - very high mag. (WC/Nephron)]]
|-
| Plexiform
| web-like formation<ref>URL: [http://www.mondofacto.com/facts/dictionary?plexiform http://www.mondofacto.com/facts/dictionary?plexiform]. Accessed on: March 9, 2010.</ref>
| [[plexiform neurofibroma]], [[MPNST]], plexiform lesion of [[pulmonary hypertension]]
| [http://www.flickr.com/photos/bc_the_path/1715728630/ plexiform lesion of Pulm. HTn (flickr.com)]
|-
| Cribriform
| pierced with small holes<ref>URL: [http://dictionary.reference.com/browse/cribriform http://dictionary.reference.com/browse/cribriform]. Accessed on: 8 August 2011.</ref>
| cribriform [[DCIS]], cribriform [[HGPIN]], cribriforming in a [[tubular adenoma of the gastrointestinal tract|tubular adenoma]] with high-grade dysplasia, endometrioid endometrial carcinoma
| [[Image:Atypical_ductal_hyperplasia_-_very_high_mag.jpg|thumb|center|150px|Cribriform architecure ([[ADH]]) - very high mag. (WC/Nephron)]]
|-
| Solid ''or'' Sheeting
| no architecture - back-to-back cells with no pattern apparent / no spaces between cells
| solid DCIS, poorly-differentiated malignancy (carcinoma, sarcoma, lymphoma)
| [[Image:Merkel_cell_carcinoma_-_high_mag.jpg|thumb|center|150px|Sheeting in a [[Merkel cell carcinoma]] - high mag. (WC/Nephron)]]
|-
| Micropapillary
| nipple like projections without a fibrovascular core (papillary = nipple-like<ref>URL: [http://dictionary.reference.com/browse/papillary http://dictionary.reference.com/browse/papillary]. Accessed on: 8 August 2011.</ref>)
| micropapillary [[DCIS]], micropapillary [[HGPIN]]
| [http://www.breastpathology.info/Sloane/Images/dcis/micropap1-400.jpg micropapillary DCIS (breastpathology.info)]<ref name=sloane/>
|-
| Papillary
| nipple-like projection with a fibrovascular core
| [[papillary thyroid carcinoma]]
| [[Image:Papillary_renal_cell_carcinoma_high_mag.jpg| thumb|center|150px|[[Papillary RCC]] - high mag. (WC/Nephron)]]
|-
| Flat
| board-like, does not have a projection above the surface
| flat DCIS
| [http://www.breastpathology.info/Sloane/Images/dcis/flat1-400.jpg flat DCIS 1 (breastpathology.info)],<ref name=sloane/> [http://www.breastpathology.info/Sloane/Images/dcis/flat2-400.jpg flat DCIS 2 (breastpathology.info)]<ref name=sloane>URL: [http://www.breastpathology.info/Sloane/dcis.html http://www.breastpathology.info/Sloane/dcis.html]. Accessed on: 8 August 2011.</ref>
|-
| Herring bone
| like herring bone (technique) for climbing a hill in cross country skiing; books on a shelf, where they have partially fallen over -- on the one shelf to the left and the one below to the right
| [[fibrosarcoma]], [[synovial sarcoma]], [[MPNST]]
| [[Image:Malignant_peripheral_nerve_sheath_tumour_-_high_mag.jpg|thumb|center|150px| MPNST - high mag.(WC/Nephron)]]
|-
| [[Trabecular]] ''or'' cords
| trabecula = ''little beam''<ref>URL: [http://dictionary.reference.com/browse/trabecula http://dictionary.reference.com/browse/trabecula]. Accessed on: 26 December 2010.</ref>; quasi-linear arrangement of cells
| normal liver lobule, [[Sertoli cell tumour]]
| [[Image:Papillary thyroid carcinoma tall cell var high mag.jpg|thumb|center|150px|PTC tall cell variant - high mag. (WC/Nephron)]]
|-
| Nested (nesting)
| islands of cells with a circular outline
| neuroendocrine tumours
| [[Image:Small_intestine_neuroendocrine_tumour_high_mag_cropped.jpg |thumb|center|150px|Neuroendocrine tumour - low mag. (WC/Nephron)]]
|-
| Biphasic / multiple patterns
| multiple patterns or cell types; e.g. spindle cells and epithelioid cells
| [[synovial sarcoma]], [[malignant melanoma]], [[pleomorphic adenoma]], [[angiomyolipoma]], [[chondroid syringoma]]
| [[Image:Desmoplastic_small_round_cell_tumour_-_high_mag.jpg |thumb|center|150px| DSRCT - high mag. (WC/Nephron)]]
|}


===Nuclear destruction words===
===Nuclear destruction words===
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Image:
Image:
*[http://commons.wikimedia.org/wiki/File:Ulcers,_fissures,_and_erosions.svg Ulcers and erosions - schematic (WC)].
<gallery>
 
Image:Ulcers,_fissures,_and_erosions.svg | Ulcers and erosions - schematic. (WC)
</gallery>
====Microscopic - erosion====
====Microscopic - erosion====
Features - require 1 and 2:
Features - require 1 and 2:
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*Benign soft tissue lesions may have marked [[nuclear atypia]] and abundant mitotic activity.
*Benign soft tissue lesions may have marked [[nuclear atypia]] and abundant mitotic activity.


===Basic pathologic differential diagnosis of malignancy===
===General differential diagnosis of malignant lesion===
This should ''always'' be considered:
This should ''always'' be considered:
<center>
<center>
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Q. Why? <br>
Q. Why? <br>
A. (1) The site of the tumour can considerably change the differential diagnosis. (2) The management is usually totally different.<br><br>
A. (1) The site of the tumour can considerably change the differential diagnosis. (2) The management is usually totally different.<br><br>
A clinically motivated histomorphologic classification of malignancy:
 
===A general clinico-histomorphologically motivated differential diagnosis of malignancy===
<center>
<center>
<!--
<!--
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*''[[Malignant melanoma]]'', also ''melanoma'', is a separate category as it can look like almost anything under the microscope.
*''[[Malignant melanoma]]'', also ''melanoma'', is a separate category as it can look like almost anything under the microscope.
*''Hematologic'' includes [[lymphoma]], [[leukemia]], [[plasma cell neoplasms]] and others.
*''Hematologic'' includes [[lymphoma]], [[leukemia]], [[plasma cell neoplasms]] and others.
*The above is a useful clinical classification. The problem is it isn't that useful for difficult cases as:
**Germ cell tumours are often not distinctive.
**Numerous epithelioid sarcomas can mimic carcinomas.
**Spindle cell carcinomas can mimic sarcomas very well.
**Neuroendocrine differentiation  is not always readily apparent.
**The ''[[modified general morphologic DDx of malignancy]]'' is better for approaching difficult tumours.
Memory device ''HMN GEM'': hematologic, melanoma, neuroendocrine carcinoma, germ cell, epithelial, mesenchymal.


===Morphologic grouping===
====Morphologic categorization====
=====Factors to consider=====
Factors to consider when attempting to group by morphology:
Factors to consider when attempting to group by morphology:
#Cell shape (spindle cell, epithelioid, plasmacytoid, mixed).
#Cell size (small or large) - size in relation to a neutrophil or [[red blood cell]].
#Cell cohesion - dyscohesive vs. cohesive.
#Cell cohesion - dyscohesive vs. cohesive.
#*If one sees several groups of 5+ cells... probably cohesive.
#*If one sees several groups of 5+ cells... probably cohesive.
#*Presence of cell cohesion strongly disfavours lymphoma.
#*Presence of cell cohesion strongly disfavours lymphoma.
#Cell size - in relation to a neutrophil or red blood cell.
#Cytoplasm - abundance (scant, moderate, abundant).
#Cytoplasm - abundance (scant, moderate, abundant).
#*Eosinophilic cytoplasm disfavours lymphoma.
#*Eosinophilic cytoplasm disfavours lymphoma.
#*Oncocytic - possessing copious eosinophilic granular cytoplasm.
#**Benign lesions composed of oncocytes - oncocytoma
#**Oncocytic metaplasia (alteration of cytoplasm) can effect all or a part of a lesion.
#**Oncocytic neoplasms are common in the kidneys, thyroid and salivary glands.
#**Oncocytic change increases with age
#**May represent senescent accumulation of mitochondria in secretory epithelial.
#Chromatin - coarseness (fine, granular).
#Chromatin - coarseness (fine, granular).
#Nucleoli - number (absent, present, multiple).
#Nucleoli - number (absent, present, multiple).
#*Large [[nucleoli]] (nucleoli seen with the 10x objective) pretty much exclude neuroendocrine.
#*Large [[nucleoli]] (nucleoli seen with the 10x objective) pretty much exclude neuroendocrine.


Probable category by morphology:
======Types of cells======
*Carcinoma = cohesive, relatively large (>~2X neutrophil), +/-nucleolus, +/-gland formation (circular structures), often moderate to abundant cytoplasm.
{| class="wikitable sortable"
*Sarcoma = cohesive, composed of spindle cells (cells taper at both ends, nucleus oval/cigar-shaped).
! Type
*Germ cell tumour = appearance often similar to ''carcinoma''.
! Morphology
*Neuroendocrine carcinoma = cohesive, fine granular chromatin and no nucleolus.
! Significance
*Lymphoma = dyscohesive, relatively small (usually <=2X neutrophil diameter), usu. scant basophilic (blue) cytoplasm.
|-
*Melanoma = classically pigmented, often a prominent [[red nucleolus]], a mix of spindle cells and epithelioid cells, mix of cohesive and dyscohesive cells.
| [[Spindle cell]]
| tapered at both ends<ref>URL: [http://www.medterms.com/script/main/art.asp?articlekey=25657 http://www.medterms.com/script/main/art.asp?articlekey=25657]. Accessed on: 18 January 2010.</ref>
| suggestive of sarcoma - compatible with melanoma and some carcinomas
|-
| Epithelioid cell
| cell shape round/oval, nucleus round/oval, looks like epithelium (cell borders touch neighbouring cells - collectively form a barrier)
| suggests epithelial lesion (carcinoma) - compatible with others
|-
| [[Small round blue cell tumour]]/lymphoid:
| small cells with scant cytoplasm - usually round; "small" is classically 2x a "resting lymphocyte" diameter †
| common in children; in adults often lymphoma
|-
| Small lymphoid ([[small cell lymphoma]]).
| "small" in the context of lymphoid is classically ~1x a "resting lymphocyte" diameter; often not malignant by cytology
| suggests [[small cell lymphoma]], reactive changes or infection
|-
| Plasmacytoid cell
| resemble a plasma cell: eccentric nucleus, moderate basophilic cytoplasm, +/-"clockface" chromatin pattern (clumping of chromatin at the periphery of the nucleus), +/-perinuclear hof (crescentic cytoplasmic clearing adjacent to the nucleus; represents abundant Golgi apparatus
| suggests [[plasma cell neoplasm]] or infection
|}
 
Note:
*† Diameter of a "resting lymphocyte" ~ diameter of a [[red blood cell]] (RBC) ~ 8 micrometres.
**Most carcinoma cells are 3-4x the size of a RBC.


====Dyscohesive vs. cohesive====
======Dyscohesive versus cohesive======
Deciding cells are dyscohesive vs. cohesive is important, as it is a strong determinant of whether one is dealing with a lymphoid lesion or not.
Deciding cells are dyscohesive vs. cohesive is important, as it is a strong determinant of whether one is dealing with a lymphoid lesion or not.


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*Basophilic cytoplasm.
*Basophilic cytoplasm.


===Histomorphologic classification===
=====Probable category by morphology=====
Types of cells:
*Carcinoma = cohesive, relatively large (>~2X neutrophil), +/-nucleolus, +/-gland formation (circular structures), often moderate to abundant cytoplasm.
*[[Spindle cell]]:
*Sarcoma = cohesive, composed of spindle cells (cells taper at both ends, nucleus oval/cigar-shaped).
**Tapered at both ends.<ref>URL: [http://www.medterms.com/script/main/art.asp?articlekey=25657 http://www.medterms.com/script/main/art.asp?articlekey=25657]. Accessed on: 18 January 2010.</ref>
*Germ cell tumour = appearance often similar to ''carcinoma'', site (location) very useful - esp. gonadal, midline, retroperitoneal.
**Suggests mesenchyme, i.e. sarcoma, compatible with melanoma and some carcinomas.
*[[Neuroendocrine carcinoma]] = cohesive, fine granular chromatin and no [[nucleolus]].
*Plasmacytoid cell.
*Lymphoma = dyscohesive, relatively small (usually <=2X neutrophil diameter), usu. scant basophilic (blue) cytoplasm.
**Resemble a plasma cell: eccentric nucleus, moderate basophilic cytoplasm, +/-"clockface" chromatin pattern (clumping of chromatin at the periphery of the nucleus), +/-perinuclear hof (crescentic cytoplasmic clearing adjacent to the nucleus; represents abundant Golgi apparatus).  
*Melanoma = classically pigmented, often a prominent [[red nucleolus]], a mix of spindle cells and epithelioid cells, mix of cohesive and dyscohesive cells.
*Epithelioid cell.
 
**Looks like epithelium - cell borders touch neighbouring cells so that the cells collectively form a barrier.
===A practical histomorphologic differential diagnosis of malignancy===
*[[Small round blue cell tumour]]/lymphoid:
====General morphologic DDx of malignancy====
**Small cells with scant cytoplasm.
{{familytree/start}}                     
***"Small" is classically 2x a "resting lymphocyte" diameter.
{{familytree  | | | | | | | A01 | | | | | | | | A01=Malignancy}}
****Diameter of a "resting lymphocyte" ~ diameter of a [[red blood cell]] (RBC) ~ 8 micrometres.
{{familytree  | |,|-|-|-|v|-|^|-|v|-|-|-|.| | |}}
****Most carcinoma cells are 3-4x the size of a RBC.
{{familytree  | B01 | | B02 | | B03 | | B04 | |B01=[[Large epithelioid tumours]]|B02=[[spindle cell lesions|Spindle cell tumours]]|B03=[[small round cell tumours|Small blue cell tumours]]|B04=[[Pleomorphic tumours]]}}
*Small lymphoid ([[small cell lymphoma]]).
{{familytree/end}}
**"Small" in the context of lymphoid is classically ~1x a "resting lymphocyte" diameter.
 
**Often not malignant by cytology.
====Modified general morphologic DDx of malignancy====
<center>
{{familytree/start}}
{{familytree | | | | | | | | | | | A | | | | | | | | | | |A=Malignancy}}
{{familytree | |,|-|-|-|v|-|-|-|v|-|^|-|v|-|-|-|v|-|-|-|.| |}}
{{familytree | B | | C | | D | | E | | F | |G |B=[[Large epithelioid tumours]]|C=[[spindle cell lesions|Spindle cell tumours]]|D=[[small round cell tumours|Small blue cell tumours]]|E=[[Pleomorphic tumours]]|F=[[Clear cell tumours]]|G=[[myxoid lesions|Myxoid tumours]]}}
{{familytree/end}}
</center>
 
The above is more useful than the ''general clinico-histomorphologically motivated differential diagnosis of malignancy''.


==Differential diagnosis by site==
==Differential diagnosis by site==
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*Apoptotic cell -- has nuclear condensation (pyknosis), eosinophilic cytoplasm.
*Apoptotic cell -- has nuclear condensation (pyknosis), eosinophilic cytoplasm.


Images:
====Images====
<gallery>
Image:Atypical_mitosis.jpg| Mitoses and an atypical mitosis. (WC)
Image:Tripolar_Mitosis_-_breast_carcinoma.jpg| Tripolar mitosis. (WC)
</gallery>
www:
*[http://education.vetmed.vt.edu/Curriculum/VM8054/Labs/Lab4/IMAGES/MITOSIS%20IN%20GUT.JPG Mitoses (vetmed.vt.edu)].
*[http://education.vetmed.vt.edu/Curriculum/VM8054/Labs/Lab4/IMAGES/MITOSIS%20IN%20GUT.JPG Mitoses (vetmed.vt.edu)].
*[http://commons.wikimedia.org/wiki/File:Atypical_mitosis.jpg Mitoses and an atypical mitosis (WC)].
*[http://commons.wikimedia.org/wiki/File:Tripolar_Mitosis_-_breast_carcinoma.jpg Tripolar mitosis (WC)].
*[http://www.flickr.com/photos/euthman/426956752/ Starburst mitosis (flicker.com)].
*[http://www.flickr.com/photos/euthman/426956752/ Starburst mitosis (flicker.com)].


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*A collection of PMNs... think about ''necrosis'' and ''abscess''.
*A collection of PMNs... think about ''necrosis'' and ''abscess''.


===Lymph node metstatsis===
===Lymph node metastasis===
{{Main|Lymph node metastasis}}
{{Main|Lymph node metastasis}}
*Take a good to look at the tumour first.
*Take a good to look at the tumour first.
*Tumour in a node is often better differentiated than the most poorly differentiated part in the primary site.
*Tumour in a node is often better differentiated than the most poorly differentiated part in the primary site.
*Subcapsular space - the first place to look for mets.
*Subcapsular space - the first place to look for mets.
*Lymph node metstasis are usually obvious.
*Lymph node metastasis are usually obvious.
**There are of course exceptions, e.g. [[small cell carcinoma]], [[invasive lobular carcinoma]].
**There are of course exceptions, e.g. [[small cell carcinoma]], [[invasive lobular carcinoma]].
*Histiocytes may be difficult to separate from tumour - especially for the novice.
*Histiocytes may be difficult to separate from tumour - especially for the novice.
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*Alican blue-PAS stain.
*Alican blue-PAS stain.


Images:
====Images====
<gallery>
Image:Signet_ring_cells_5.jpg |SRCs - H&E stain. (WC/Nephron)
Image:Gastric_signet_ring_cell_carcinoma_histopatholgy_(2)_PAS_stain.jpg | SRCs - AL-PAS stain. (WC)
Image:Gastric_signet_ring_cell_carcinoma_histopatholgy_(1).jpg | SRC - H&E stain. (WC)
</gallery>
www:
*[http://www.engravingarts.com/sales/LVX2.jpg Signet rings (engravingarts.com)].
*[http://www.engravingarts.com/sales/LVX2.jpg Signet rings (engravingarts.com)].
*[http://commons.wikimedia.org/wiki/File:Signet_ring_cells_5.jpg SRCs (H&E) (WC/Nephron)].
 
*[http://commons.wikimedia.org/wiki/File:Gastric_signet_ring_cell_carcinoma_histopatholgy_(2)_PAS_stain.jpg SRC AL-PAS stain (WC)].
*[http://commons.wikimedia.org/wiki/File:Gastric_signet_ring_cell_carcinoma_histopatholgy_(1).jpg SRC H&E stain (WC)].


===Necrosis===
===Necrosis===
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*[http://www.nature.com/bmt/journal/v39/n9/fig_tab/1705646f1.html Necrosis (nature.com)].
*[http://www.nature.com/bmt/journal/v39/n9/fig_tab/1705646f1.html Necrosis (nature.com)].
*[http://moon.ouhsc.edu/kfung/jty1/Com08/Com08Image/Com801-1-09.gif Necrosis (ouhsc.edu)].<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/Com08/Com801-1-Diss.htm http://moon.ouhsc.edu/kfung/jty1/Com08/Com801-1-Diss.htm]. Accessed on: 3 November 2010.</ref>
*[http://moon.ouhsc.edu/kfung/jty1/Com08/Com08Image/Com801-1-09.gif Necrosis (ouhsc.edu)].<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/Com08/Com801-1-Diss.htm http://moon.ouhsc.edu/kfung/jty1/Com08/Com801-1-Diss.htm]. Accessed on: 3 November 2010.</ref>
*[http://commons.wikimedia.org/wiki/File:Cat_scratch_disease_-_very_high_mag.jpg Necrosis in cat scratch disease (WC)].
<gallery>
*[http://commons.wikimedia.org/wiki/File:Histiocytic_necrotizing_lymphadenitis_-_very_high_mag.jpg Necrosis in histiocytic necrotizing lymphadenitis (WC)].
Image:Cat_scratch_disease_-_very_high_mag.jpg | Necrosis in [[cat scratch disease]]. (WC/Nephron)
*[http://commons.wikimedia.org/wiki/File:Systemic_lupus_erythematosus_lymphadenopathy_-_high_mag.jpg Necrosis in SLE lymphadenopathy (WC)].
Image:Histiocytic_necrotizing_lymphadenitis_-_very_high_mag.jpg | Necrosis in [[histiocytic necrotizing lymphadenitis]]. (WC/Nephron)
Image:Systemic_lupus_erythematosus_lymphadenopathy_-_high_mag.jpg | Necrosis in [[SLE lymphadenopathy]]. (WC/Nephron)
</gallery>


==Granulomas==
==Granulomas==
*Granulomas can be elusive to the novice.
{{Main|Granuloma}}
*Plural of ''granuloma'' was ''granulomata''; ''granulomas'' (an anglicized version) is, however, now generally accepted.
 
===Definition of granuloma===
*Many definitions exist.
*The term is used rather loosely by clinicans.
**Radiologists occasionally call small lung nodules "granulomas".
 
====Strict pathologic definition====
Robbins definition:
*Chronic inflammatory reaction characterized by the focal accumulation of activated macrophages, often with an epithelioid appearance.<ref name=Ref_PBoD82>{{Ref PBoD|82}}</ref>
**"Epithelioid" cells = cells whose morphology resembles that of epithelial cells; the cells appear to adhere to one another.
 
Adams definition - it's short & sweet:
*A compact collection of macrophages.<ref name=pmid937513>{{cite journal |author=Adams DO |title=The granulomatous inflammatory response. A review.  |journal=American Journal of Pathology |volume=84 |issue=1 |pages=164&ndash;191 |year=1976 |pmid=937513 |doi= |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2032357/?tool=pubmed}}</ref>
**The macrophages must form a small ball/cluster of cells, i.e. touch one another.
 
Other pathologic definitions include the presence of:<ref name=pmid937513/>
*Plasma cells.
*Lymphocytes.
*Epithelioid macrophages.
 
Notes:
*The textbook answer for what is a granuloma is: "A collection of epitheliod macrophages."
**Granulomas are often associated with lymphocytes.
 
===Features that assist one in finding granulomas===
#Collection of cells that have abundant bubbly cytoplasm - '''most useful feature'''.
#*Image: [http://commons.wikimedia.org/wiki/File:Granuloma_20x.jpg Granulomas showing abundant bubbly cytoplasm (WC)].
#'''Multinucleated [[giant cells]]''' - these are easy to identify if you've seen some before.
#*Individual/singular multinucleated giant cells are not diagnostic of a granuloma... but should raise one's suspicion of one being present.
#*Image: [http://commons.wikimedia.org/wiki/File:Asteroid_body_intermed_mag.jpg Granulomas with multinucleated giant cells in sarcoidosis (WC)].
#Necrosis - too much pink (on H&E stained sections).
#*Image: [http://commons.wikimedia.org/wiki/File:Necrogran10x.jpg Granuloma with necrosis (WC)].
 
Notes:
*Small round collection of lymphocytes - without a capsule (as seen in lymph nodes).
**If there are no macrophages... it's a ''lymphoid nodule''.
 
====As a list====
Features:<ref>GS. 26 January 2010.</ref>
#Foamy/bubbly cytoplasm, abundant - '''low power'''.
#Epithelioid morphology - cell borders ''near'' indistinct - '''key feature'''.
#"Footprint" pattern nuclei/bean-shaped nuclei - '''key feature'''.
#*Macrophages usu. have an ovoid nucleus.
#+/-Nucleoli, small.
#+/-Fibrosis.
#+/-Palisading at edge.
 
====DDx====
*Reactive germinal centre - especially if there are abundant surrounding lymphocytes.<ref name=Ref_GLP170>{{Ref GLP|170}}</ref>
 
===Classification of granuloma===
====Histologic classification====
#Necrosing (also ''caseating'').
#*More likely to be infectious.
#*Examples: [[Tuberculosis]] (TB).
#Non-necrosing.
#*Less likely to be infectious.
#*Examples: Crohn's disease, sarcoidosis, drug reaction.
 
Whether necrosis is present in a granuloma is affected by the immune function, e.g. a [[HIV]]/AIDS patient may have non-necrosing granulomata due to TB.
 
Notes:
*A few people differentiate between ''caseating'' (fragments of recognizable tissue) and ''necrosing'' (dead debris only).<ref name=pmid17257125>{{Cite journal  | last1 = El-Zammar | first1 = OA. | last2 = Katzenstein | first2 = AL. | title = Pathological diagnosis of granulomatous lung disease: a review. | journal = Histopathology | volume = 50 | issue = 3 | pages = 289-310 | month = Feb | year = 2007 | doi = 10.1111/j.1365-2559.2006.02546.x | PMID = 17257125 }}</ref>
*Infectious non-necrosing infections: [[Mycobacterium avium complex]] (MAC), [[cryptococcus]], infections in immunosuppressed individuals.<ref name=pmid17257125/>
 
====Etiologic classification====
#Infectious, e.g. [[tuberculosis]], [[MAC]], [[leprosy]], [[syphilis]], [[cat-scratch disease]], schistosomiasis,<ref name=Ref_PCPBoD8_47>{{Ref PCPBoD8|47}}</ref> fungal infection.
#Neoplastic, e.g. [[seminoma]], Lennert lymphoma,<ref name=pmid19775391>{{Cite journal  | last1 = Summers | first1 = TA. | last2 = Rush | first2 = W. | last3 = Aguilera | first3 = N. | last4 = Lupton | first4 = G. | title = Cutaneous involvement in the lymphoepithelioid variant of peripheral T-cell lymphoma, unspecified (Lennert lymphoma). Report of a case and review of the literature. | journal = J Cutan Pathol | volume = 36 Suppl 1 | issue =  | pages = 25-30 | month = Oct | year = 2009 | doi = 10.1111/j.1600-0560.2008.01203.x | PMID = 19775391 }}</ref> ruptured ovarian teratoma.<ref name=pmid15526210>{{Cite journal  | last1 = Phupong | first1 = V. | last2 = Sueblinvong | first2 = T. | last3 = Triratanachat | first3 = S. | title = Ovarian teratoma with diffused peritoneal reactions mimicking advanced ovarian malignancy. | journal = Arch Gynecol Obstet | volume = 270 | issue = 3 | pages = 189-91 | month = Nov | year = 2004 | doi = 10.1007/s00404-003-0479-8 | PMID = 15526210 }}</ref>
#Autoimmune/inflammatory, e.g. [[Wegener's granulomatosis]], [[Churg-Strauss syndrome]].
#Allergic, e.g. [[hypersensitivity pneumonitis]].
#Foreign body, e.g. pulmonary talcosis, silicosis, berylliosis.<ref name=Ref_PCPBoD8_47>{{Ref PCPBoD8|47}}</ref>
#Drug reaction.
#Idiopathic, e.g. [[sarcoidosis]].
 
Notes:
*Memory device: ''DNF AAII'' = drug reaction, neoplasm, foreign body, allergy, autoimmune, idiopathic, infection.
*A long [[DDx]] for granulomas is complied by ''James''.<ref name=pmid10908370>{{Cite journal  | last1 = James | first1 = DG. | title = A clinicopathological classification of granulomatous disorders. | journal = Postgrad Med J | volume = 76 | issue = 898 | pages = 457-65 | month = Aug | year = 2000 | doi =  | PMID = 10908370 }}</ref>
 
===Lung granulomata===
There are many causes.<ref name=pmid17257125/>
 
Infectious:
*Myocbacterial: [[Tuberculosis]], [[MAC]], other.
*Fungal: [[Histoplasmosis]], [[Cryptococcosis]], [[Blastomycosis]], [[Coccidioidomycosis]].
*[[Aspiration pneumonia]].
Non-infectious:
*Pneumoconioses/[[hypersensitivity pneumonitis]]: Talcosis, Berylliosis.
Idiopathic/autoimmune:
*[[Sarcoidosis]].
*[[Wegener's granulomatosis]].
*[[Churg-Strauss disease]].
*[[Rheumatoid nodules]].
 
===Special granulomas===
====Fibrin ring granuloma====
*Classically associated with ''[[Q fever]]''.
**DDx:<ref name=pmid11881318>{{cite journal |author=Tjwa M, De Hertogh G, Neuville B, Roskams T, Nevens F, Van Steenbergen W |title=Hepatic fibrin-ring granulomas in granulomatous hepatitis: report of four cases and review of the literature |journal=Acta Clin Belg |volume=56 |issue=6 |pages=341–8 |year=2001 |pmid=11881318 |doi= |url=}}</ref> infections (Coxiella burnetii (causes [[Q fever]]), [[CMV]], [[EBV]] + others), drug reaction, malignancy (e.g. Hodgkin lymphoma<ref name=pmid8514044>{{cite journal |author=de Bayser L, Roblot P, Ramassamy A, Silvain C, Levillain P, Becq-Giraudon B |title=Hepatic fibrin-ring granulomas in giant cell arteritis |journal=Gastroenterology |volume=105 |issue=1 |pages=272–3 |year=1993 |month=July |pmid=8514044 |doi= |url=}}</ref>).
*Appearance:
**Epithelioid macrophages (i.e. a granuloma) surrounding a fibrin ring with a clear (lipid-filled) vacuole at its center.
***Images:
****[http://en.gooword.com/picture/864449/ FRG (gooword.com)].


==Common morphologic problems==
==Common morphologic problems==
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*'''S'''mooth muscle cells (SMCs).
*'''S'''mooth muscle cells (SMCs).


Images:
=====Images=====
*[http://commons.wikimedia.org/wiki/File:Ovarian_fibroma_-_high_mag.jpg Collagen - ovarian fibroma (WC)].
<gallery>
*[http://commons.wikimedia.org/wiki/File:Cardiac_amyloidosis_high_mag_he.jpg Amyloid - cardiac amyloidosis (WC)].
Image:Cardiac_amyloidosis_high_mag_he.jpg | Cardiac amyloid. (WC/Nephron)
Image:Laminations_in_a_thrombus_-_high_mag.jpg | Fibrin in a thrombus. (WC/Nephron)
Image:Ovarian_fibroma_-_high_mag.jpg | Collagen in an ovarian fibroma. (WC/Nephron)
Image:Glatte_Muskelzellen.jpg | Smooth muscle. (WC/Polarlys)
</gallery>


====Smooth muscle cells (SMCs) vs. fibrous tissue====
====Smooth muscle cells (SMCs) vs. fibrous tissue====
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Note:
Note:
*Most of the resident [[microscope]]s, at U of T, have an eye piece diameter of 22 mm. Therefore, the field diameter at 40 X is approximately 22 mm / 40 X ~= 0.55 mm and the field of view is pi/4*(0.55 mm)^2 = 0.2376 mm^2.
*Most modern [[microscope]]s, have an eye piece diameter of 22 mm. Therefore, the field diameter at 40 X is approximately 22 mm / 40 X ~= 0.55 mm and the field of view is pi/4*(0.55 mm)^2 = 0.2376 mm^2.


==Pathology reports==
==Pathology reports==
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==Lab talk==
==Lab talk==
{{Main|Cutting}}
Tissue cutting terms - these often vary from lab-to-lab:<ref>URL: [http://www.mailman.srv.ualberta.ca/pipermail/patho-l/2002-July/016955.html http://www.mailman.srv.ualberta.ca/pipermail/patho-l/2002-July/016955.html]. Accessed on: 18 October 2011.</ref>
Tissue cutting terms - these often vary from lab-to-lab:<ref>URL: [http://www.mailman.srv.ualberta.ca/pipermail/patho-l/2002-July/016955.html http://www.mailman.srv.ualberta.ca/pipermail/patho-l/2002-July/016955.html]. Accessed on: 18 October 2011.</ref>
*Recut = cut off the top of the block.
*Recut = cut off the top of the block.
Michael
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