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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]]).
*Too much '''BLUE''' = BAD.
*Too much '''BLUE''' = BAD.


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==
===Very common===
===Staining===
*Eosinophilic - pink.
*Eosinophilic - pink.
*Hyperchromatic - blue.
*Hyperchromatic - blue.
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**''Amphophilic'' means stains with both acidic & basic dyes.
**''Amphophilic'' means stains with both acidic & basic dyes.
**Images: [http://pancreaticcancer2000.com/immunoblast1.jpg amphophilic material - arrow (pancreaticcancer2000.com)], [http://www.webpathology.com/image.asp?n=4&Case=20 amphophilic cytoplasm in prostate carcinoma (webpathology.com)].
**Images: [http://pancreaticcancer2000.com/immunoblast1.jpg amphophilic material - arrow (pancreaticcancer2000.com)], [http://www.webpathology.com/image.asp?n=4&Case=20 amphophilic cytoplasm in prostate carcinoma (webpathology.com)].
 
*''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.
===Less common===
===Morphologic patterns===
*Hobnail - basement membrane area < area exposed to luminal surface.
{{Main|Morphologic patterns}}
*Storiform - spiral appearance or cartwheel pattern<ref>Storiform. dictionary.com. URL: [http://dictionary.reference.com/browse/storiform http://dictionary.reference.com/browse/storiform]. Accessed on: April 24, 2009.</ref>
This covers things like ''cribriform'', ''hobnail'', ''herring bone'' and many others.
**Images: [http://cal.vet.upenn.edu/projects/derm/Home/UNCLASS/heman.htm Storiform pattern (upenn.edu)], [http://www.ispub.com/journal/the_internet_journal_of_pathology/volume_8_number_1_13/article/sarcomatous_transformation_in_an_inflammatory_myofibroblastic_tumor_of_lung_a_rare_finding_in_a_young_male-4.html Storiform pattern (ispub.com)].
*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>


===Nuclear destruction words===
===Nuclear destruction words===
Line 33: Line 43:


Image:  
Image:  
*[http://upload.wikimedia.org/wikipedia/en/5/51/Nuclear_changes.jpg Karyolysis, pyknosis, karyorrhexis (wikimedia.org)].
*[http://en.wikipedia.org/wiki/File:Nuclear_changes.jpg Karyolysis, pyknosis, karyorrhexis (WP)].
 
===Erosions and ulcers===
*Ulcer = lesion through skin or mucous membrane.
*Erosion = limited to the mucosa - superficial ulceration.
**In dermatopathology - through the epidermis.
 
Image:
<gallery>
Image:Ulcers,_fissures,_and_erosions.svg | Ulcers and erosions - schematic. (WC)
</gallery>
====Microscopic - erosion====
Features - require 1 and 2:
#Loss of epithelium.
#Vital response at site of lost epithelium.
#*[[Neutrophil]]ic infiltrate.
#*+/-Fibrin.
#*+/-Cellular debris.


==DDx in medicine==
Image:
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400158/figure/f4-cln_67p705/ Mucosal erosion (nih.gov)].<ref name=pmid22892912>{{Cite journal  | last1 = Arashiro | first1 = RT. | last2 = Teixeira | first2 = MG. | last3 = Rawet | first3 = V. | last4 = Quintanilha | first4 = AG. | last5 = Paula | first5 = HM. | last6 = Silva | first6 = AZ. | last7 = Nahas | first7 = SC. | last8 = Cecconello | first8 = I. | title = Histopathological evaluation and risk factors related to the development of pouchitis in patients with ileal pouches for ulcerative colitis. | journal = Clinics (Sao Paulo) | volume = 67 | issue = 7 | pages = 705-10 | month = Jul | year = 2012 | doi =  | PMID = 22892912 | PMC = 3400158 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400158/}}</ref>
 
==The general differential diagnosis==
Mnemonic ''CINE-TV-DATE'':
Mnemonic ''CINE-TV-DATE'':
*Congenital.
*Congenital.
Line 50: Line 80:
In diagnostic pathology, most stuff falls into the ''neoplastic'' category.
In diagnostic pathology, most stuff falls into the ''neoplastic'' category.


===Basic pathologic [[DDx]] of malignancy===
===Features of malignancy===
====Cytologic features of malignancy====
It is said that:<ref name=boerner>S. Boerner. 12 September 2011.</ref>
#It is the nuclear abnormalities that make a cell malignant.
#The cytoplasm that gives one clues as to the cell of origin.
 
Nuclear features and malignancy:<ref name=boerner>S. Boerner. 12 September 2011.</ref>
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Feature
! Strength in predicting malignancy?
|-
| Large nuclear size
| weak
|-
| [[Nuclear-to-cytoplasmic ratio]]
| strong
|-
| Nuclear pleomorphism
| weak
|-
| Nucleoli shape (angulated, spiked, complex)
| strong
|-
| Nucleoli size
| weak - generally; strong if like in a [[Hodgkin lymphoma|RS cell]]
|-
| High nucleoli number
| weak negative; finding favours benign
|-
| Chromatin hyperchromasia
| weak
|-
| Chromatin granularity
| strong
|-
| Nuclear membrane irregularities
| strong (clefting, flat edges, sharp angles), <br>scalloped (suggests benign)
|-
| Mitoses
| weak §
|-
| Atypical mitoses
| strong
|}
 
§ mitoses are seen in poorly differentiated tumour and regeneration.  High mitotic rate in the context of unremarkable nuclear morphology is usually not malignant.
 
====Other features====
In the context of [[soft tissue lesions]], it is said that the two most important features of malignancy are:
#[[Necrosis]].
#High vascularity.
 
Notes:
*Benign soft tissue lesions may have marked [[nuclear atypia]] and abundant mitotic activity.
 
===General differential diagnosis of malignant lesion===
This should ''always'' be considered:
<center>
<!--
DDX OF MALIGNANCY - FIRST STEP
-->
{{familytree/start}}
{{familytree | | | |A11| | | | |A11 = Malignancy          }}
{{familytree | |,|-|-|^|-|-|.|}}
{{familytree | B11 | | | | B12 |B11=Primary|B12=[[metastasis|Metastatic]] }}
{{familytree/end}}
</center>
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 general clinico-histomorphologically motivated differential diagnosis of malignancy===
<center>
<!--
<!--
DDX OF MALIGNANCY
DDX OF MALIGNANCY - THE NEXT STEP
-->
-->
{{familytree/start}}
{{familytree/start}}
{{familytree | | | | | | | | | | | A | | | | | | | | | | |A=Malignancy}}
{{familytree | | | | | | | | | | | A | | | | | | | | | | |A=Malignancy}}
{{familytree | |,|-|-|-|v|-|-|-|v|-|^|-|v|-|-|-|v|-|-|-|.| |}}
{{familytree | |,|-|-|-|v|-|-|-|v|-|^|-|v|-|-|-|v|-|-|-|.| |}}
{{familytree | B | | C | | D | | E | | F | |G |B=Epithelial<br>(Carcinoma)|C=Mesenchymal<br>(Sarcoma)|D=Germ cell<br>tumour|E=Neuroendocrine<br>carcinoma|F=Lymphoid<br>(Lymphoma)|G=Malignant<br>melanoma}}
{{familytree | B | | C | | D | | E | | F | |G |B=Epithelial<br>(Carcinoma)|C=Mesenchymal<br>([[Sarcoma]])|D=[[Germ cell tumours|Germ cell<br>tumour]]|E=[[Neuroendocrine carcinoma|Neuroendocrine<br>carcinoma]]|F=Hematologic|G=[[Melanoma|Malignant<br>melanoma]]}}
{{familytree/end}}
{{familytree/end}}
</center>


Notes:
Notes:
*''Melanoma'', i.e. ''malignant 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.
*''Lymphoma'' includes leukemia.
*''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.


{| class="wikitable"
{| class="wikitable sortable"
!|
!|
!| Cell spacing
!| Cell spacing
Line 128: Line 268:
*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, "clockface" chromatin pattern, scant basophilic cytoplasm.
*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]]:
====General morphologic DDx of malignancy====
**Small cells with scant cytoplasm.
{{familytree/start}}                     
{{familytree  | | | | | | | A01 | | | | | | | | A01=Malignancy}}
{{familytree  | |,|-|-|-|v|-|^|-|v|-|-|-|.| | |}}
{{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]]}}
{{familytree/end}}
 
====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==
{{Main|Short power list}}
It is essential to have a concept of what is common.  The ''[[short power list]]'' gives a short [[differential diagnosis]] for the common sites.
 
{{Main|Long power list}}
The ''[[long power list]]'' is a longer list for the common sites.


==Finding the elements==
==Finding the elements==
Line 149: Line 311:
*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)].


====Phases of mitosis====
====Phases of mitosis====
*Prophase. - chromatin condenses to chromosomes.
*Prophase - chromatin condenses to chromosomes.
*Metaphase - chromosome aligned.
*Metaphase - chromosome aligned.
*Anaphase - spindles separated.
*Anaphase - spindles separated.
Line 162: Line 327:


===Neutrophils===
===Neutrophils===
{{Main|Neutrophils}}
*Little dots = the multilobular nucleus - '''key feature'''.
*Little dots = the multilobular nucleus - '''key feature'''.
*Neutrophils are often found with friends, i.e. lymphocytes, plasma cells.
*Neutrophils are often found with friends, i.e. lymphocytes, plasma cells.
Line 174: Line 340:
*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}}
*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.
*Histiocytes may be difficult to separate from tumour - esp. initially.
**There are of course exceptions, e.g. [[small cell carcinoma]], [[invasive lobular carcinoma]].
**Histiocytes usually are in germinal centre, i.e. the node architecture helps,
*Histiocytes may be difficult to separate from tumour - especially for the novice.
**Malignant cells have to have malignant features, i.e. the NC ratio is abnormal, there is nuclear pleomorphism.
**Histiocytes may be found in the germinal centres, i.e. the node architecture helps.
**Malignant cells, generally, have to have malignant features, i.e. the [[NC ratio]] is abnormal, there is [[nuclear pleomorphism]].
*Several things can mimic metastases - see ''[[Lymph node metastasis]]''.


See: ''[[Lymph node]]'' article for a detailed description of cell types in a lymph node.
See: ''[[Lymph node]]'' article for a detailed description of cell types in a lymph node.


===Signet ring cells===
===Signet ring cell carcinoma===
Definition:
{{Main|Signet ring cell carcinoma}}
*Signet ring cells resemble [http://www.engravingarts.com/sales/LVX2.jpg signet rings (image)].
*It has been said that there are two types of pathologists... those that have missed SRCs ''and'' those that will miss SRCs.
**They contain a large amount of mucin, which pushes the nucleus to the cell periphery. The pool of mucin in a signet ring cell mimics the appearance of a finger hole and the nucleus mimics the appearance of the face of the ring in profile.


Microscopy:
Microscopic:
*Typically 2-3x the size of a lymphocyte.
*Cells resemble signet rings:
**They contain a large amount of mucin, which pushes the nucleus to the cell periphery.
**The pool of mucin in a signet ring cell mimics the appearance of a finger hole.
**The nucleus mimics the appearance of the face of the ring in profile.
*Cells typically 2-3x the size of a lymphocyte.
**Smaller than the typical adipocyte.
**Smaller than the typical adipocyte.
*Often have a [http://en.wikipedia.org/wiki/File:Crescent.svg cresentic-shaped] nucleus, or ovoid nucleus.
*Often have a crescent-shaped ''or'' ovoid nucleus.
**Capillaries sectioned on their lumen have endothelial cells-- the nuclei of these are more spindled.
**Capillaries sectioned on their lumen have endothelial cells -- the nuclei of these are more spindled.
*SRCs are usually close to friend (another SRC)
*SRCs are usually close to friend -- another SRC.
**This helps differentiate SRCs from capillaries sectioned on their lumen.
**This helps differentiate SRCs from capillaries sectioned on their lumen.
*The mucin is often clear on H&E... but maybe eosinophilic.
*The mucin is often clear on H&E... but maybe eosinophilic.
DDx:
*[[Fat atrophy]].


Stains:
Stains:
Line 203: Line 378:
*Alican blue-PAS stain.
*Alican blue-PAS stain.


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


Comment:
*It has been said that there are two types of pathologists... those that have missed SRCs ''and'' those that will miss SRCs.


===Necrosis===
===Necrosis===
{{Main|Necrosis}}
Features:
Features:
*Dead cells - pink (on H&E).
*Dead cells - pink (on H&E).
Line 226: Line 404:
*[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>PBoD P.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)].
*Necrosis - too much pink (on H&E stained sections).
**Image: [http://commons.wikimedia.org/wiki/File:Necrogran10x.jpg Granuloma with necrosis (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)].
*Small round collection of lymphocytes - without a capsule (as seen in lymph nodes).
**If there are no macrophages... it's a ''lymphoid nodule''.
 
===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, immunosuppressed individual.<ref name=pmid17257125/>
 
====Etiologic classification====
#Infectious, e.g. tuberculosis, MAC, fungal infection.
#Neoplastic, e.g. seminoma.
#Autoimmune, e.g. Wegener's granulomatosis, Churg-Strauss syndrome.
#Allergic, e.g. hypersensitivity pneumonitis.
#Foreign body, e.g. pulmonary talcosis.
#Drug reaction.
#Idiopathic, e.g. sarcoidosis.
 
Memory device: ''DNF AAII'' = drug reaction, neoplasm, foreign body, allergy, autoimmune, idiopathic, infection.
 
===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.


==Common morphologic problems==
==Common morphologic problems==
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*'''C'''ollagen (fibrous tissue).
*'''C'''ollagen (fibrous tissue).
*'''S'''mooth muscle cells (SMCs).
*'''S'''mooth muscle cells (SMCs).
=====Images=====
<gallery>
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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*Schwann cells (found in nerve): nuclei = wavy appearance, thin. (???)
*Schwann cells (found in nerve): nuclei = wavy appearance, thin. (???)


===DDx of granular crap===
===Pigmented material===
DDx of granular stuff:
*[[AKA]] brown/black granular crap.
 
DDx of granular stuff/pigment:
#Lipofuscin - especially in old people.
#Lipofuscin - especially in old people.
#Hemosiderin.
#Hemosiderin.
#Bile - found in hepatocytes, yellow.
#Bile - found in hepatocytes, yellow.
#Foreign material (tattoo pigment, anthracotic pigment).
#Foreign material (tattoo pigment, anthracotic pigment, [[amalgam tattoo]]).
#Melanin.
#Melanin.


Notes:
Notes:
*Granular stuff should prompt consideration of ''malignant melanoma''.
*Granular stuff should prompt consideration of ''malignant melanoma''.
*Memory device: '''''M'''änner '''l'''ieben '''f'''eine '''BH'''s'' = Melanin, Lipofuscin, Foreign, Bile, Hemosiderin.
*Memory device ''BH MILF''   = Bile, Homogentisic acid, Melanin, Iron (hemosiderin), Lipofuscin, Foreign material.
*''Homogentisic acid'' found in ''alkaptonuria'',<ref name=Ref_PCPBoD8_20>{{Ref PCPBoD8|20}}</ref>can be considered the sixth (black) pigment.
**Gentisic = jen-TIS-ik.<ref>URL: [http://dictionary.reference.com/browse/gentisic+acid http://dictionary.reference.com/browse/gentisic+acid]. Accessed on: 11 January 2012.</ref>


====[[Stains]] that can help sort it out====
====[[Stains]] that can help sort it out====
*Prussian blue for hemosiderin.
*Prussian blue (iron stain) for hemosiderin.
*Melan A for melanin.
*[[Fontana-Masson stain]] (or ''Melan A'') for melanin.
*Kluver-Barrera for lipofuscin.
*[[PAS stain]]<ref name=pmid5463681 >{{cite journal |author=Kovi J, Leifer C |title=Lipofuscin pigment accumulation in spontaneous mammary carcinoma of A/Jax mouse |journal=J Natl Med Assoc |volume=62 |issue=4 |pages=287–90 |year=1970 |month=July |pmid=5463681 |pmc=2611776 |doi= |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2611776/pdf/jnma00512-0077.pdf}}</ref> ''or'' Kluver-Barrera for lipofuscin.


==Staining==
==Staining==
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{{main|Pathology and food}}
{{main|Pathology and food}}


==Clinician talk==
===General surgeon talk===
*"[[R2 resection]]" = macroscopic tumour left. 
*"[[R1 resection]]" = microscopic tumour left.
*"[[R0 resection]]" = clean margin macroscopically & microscopically.


Generally, positive margins suck; in locally advanced rectal cancer survival, in one study,<ref>{{cite journal |author=Larsen SG, Wiig JN, Dueland S, Giercksky KE |title=Prognostic factors after preoperative irradiation and surgery for locally advanced rectal cancer |journal=Eur J Surg Oncol |volume=34 |issue=4 |pages=410–7 |year=2008 |month=April |pmid=17614249 |doi=10.1016/j.ejso.2007.05.012 |url=}}</ref> five year survival was found to be 60%, 31% and 0% for R0, R1, and R2 resections respectively.
==Tumour remaining==
{{Main|Surgical margins}}
''R classification'':<ref>URL: [http://www.informedicalcme.com/colon-cancer/tnm-stage-groupings/ http://www.informedicalcme.com/colon-cancer/tnm-stage-groupings/]. Accessed on: 27 March 2012.</ref>
*"RX resection" = residual tumour cannot be assessed.
*"R0 resection" = clean margin macroscopically & microscopically.
*"R1 resection" = microscopic tumour left.
*"R2 resection" = macroscopic tumour left. 
 
Surgeons use this terminology. Essentially, it is the margin status. It is nice when the surgeon's assessment and the pathologist's are in agreement.
 
Note:
*Generally, positive margins suck. For example, in locally advanced rectal cancer, in one study,<ref name=pmid17614249>{{cite journal |author=Larsen SG, Wiig JN, Dueland S, Giercksky KE |title=Prognostic factors after preoperative irradiation and surgery for locally advanced rectal cancer |journal=Eur J Surg Oncol |volume=34 |issue=4 |pages=410–7 |year=2008 |month=April |pmid=17614249 |doi=10.1016/j.ejso.2007.05.012 |url=}}</ref> five year survival was found to be 60%, 31% and 0% for R0, R1, and R2 resections respectively.


===Oncologist talk===
==Clinician talk==
===Performance status===
*ECOG - score from 1-5 for performance status.<ref name=pmid7165009>{{cite journal |author=Oken MM, Creech RH, Tormey DC, ''et al.'' |title=Toxicity and response criteria of the Eastern Cooperative Oncology Group |journal=Am. J. Clin. Oncol. |volume=5 |issue=6 |pages=649–55 |year=1982 |month=December |pmid=7165009 |doi= |url=}}</ref>
*ECOG - score from 1-5 for performance status.<ref name=pmid7165009>{{cite journal |author=Oken MM, Creech RH, Tormey DC, ''et al.'' |title=Toxicity and response criteria of the Eastern Cooperative Oncology Group |journal=Am. J. Clin. Oncol. |volume=5 |issue=6 |pages=649–55 |year=1982 |month=December |pmid=7165009 |doi= |url=}}</ref>
**ECOG =  Eastern Cooperative Oncology Group.
**ECOG =  Eastern Cooperative Oncology Group.
Line 383: Line 506:


==Pathology & pathologists==
==Pathology & pathologists==
===Fixation & lifestyle===
===[[Fixation]] & lifestyle===
Pathologist have a great lifestyle 'cause tissue takes long to fix; the penetration of tissue by formalin is 1 mm/hour.<ref>Gross rounds. 14 August 2009.</ref>
Pathologist have a great lifestyle 'cause tissue takes long to fix; the penetration of tissue by formalin is 1 mm/hour.<ref>Gross rounds. 14 August 2009.</ref>


Line 421: Line 544:
*FOV = 22 mm / 40
*FOV = 22 mm / 40
*FOV = 0.55 mm
*FOV = 0.55 mm
Note:
*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==
There is no universal standard; however, there is a push to standardize by the ''Association of Directors of Anatomic and Surgical Pathology'',<ref>URL: [http://www.adasp.org/papers/position/Standardization.htm http://www.adasp.org/papers/position/Standardization.htm]</ref> among others.
{{Main|Pathology reports}}
 
The key point in report writing is that the report should be precise, complete and easy-to-understand.  
Standards lead to uniformity and consistency.<ref name=pmid7878300>{{cite journal |author=Leslie KO, Rosai J |title=Standardization of the surgical pathology report: formats, templates, and synoptic reports |journal=Semin Diagn Pathol |volume=11 |issue=4 |pages=253–7 |year=1994 |month=November |pmid=7878300 |doi= |url=}}</ref>
 
The closest I've found to a standard is laid-out in by Goldsmith et al..<ref name=pmid18834219>Reporting guidelines for clinical laboratory reports in surgical pathology. Goldsmith JD, Siegal GP, Suster S, Wheeler TM, Brown RW. Arch Pathol Lab Med. 2008 Oct;132(10):1608-16. PMID 18834219.</ref>


===Standards===
===Standards===
As far as I know, the first papers on the topic of standards were written in 1992.<ref name=pmid1574498>{{cite journal |author=Rosai J, Bonfiglio TA, Corson JM, ''et al.'' |title=Standardization of the surgical pathology report |journal=Mod. Pathol. |volume=5 |issue=2 |pages=197–9 |year=1992 |month=March |pmid=1574498 |doi= |url=}}</ref><ref name=pmid1574486>{{cite journal |author=Frable WJ, Kempson RL, Rosai J |title=Quality assurance and quality control in anatomic pathology: standardization of the surgical pathology report |journal=Mod. Pathol. |volume=5 |issue=2 |pages=102a–102b |year=1992 |month=March |pmid=1574486 |doi= |url=}}</ref><ref>[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=PubMed&details_term=standardization,%20surgical%20pathology%20report Pubmed search]</ref>
There is no universal standard; however, there is a push to standardize by the ''Association of Directors of Anatomic and Surgical Pathology'',<ref>URL: [http://www.adasp.org/papers/position/Standardization.htm http://www.adasp.org/papers/position/Standardization.htm]</ref> among others.


====Checklists====
====Checklists====
{{Main|CAP checklists}}
The College of American Pathologists (CAP) has checklists for cancer - [http://www.cap.org/apps/cap.portal?_nfpb=true&cntvwrPtlt_actionOverride=%2Fportlets%2FcontentViewer%2Fshow&_windowLabel=cntvwrPtlt&cntvwrPtlt%7BactionForm.contentReference%7D=committees%2Fcancer%2Fcancer_protocols%2Fprotocols_index.html&_state=maximized&_pageLabel=cntvwr CAP protocols].
The College of American Pathologists (CAP) has checklists for cancer - [http://www.cap.org/apps/cap.portal?_nfpb=true&cntvwrPtlt_actionOverride=%2Fportlets%2FcontentViewer%2Fshow&_windowLabel=cntvwrPtlt&cntvwrPtlt%7BactionForm.contentReference%7D=committees%2Fcancer%2Fcancer_protocols%2Fprotocols_index.html&_state=maximized&_pageLabel=cntvwr CAP protocols].


I suspect pathologists will use more checklists in the future... they are deemed effective in a number of places inside and outside of medicine.
Pathologists will probably use more checklists in the future... they are deemed effective in a number of places inside and outside of medicine.
Surgeons know that checklists work and that they save lives.<ref name=pmid19158173>{{cite journal |author=Soar J, Peyton J, Leonard M, Pullyblank AM |title=Surgical safety checklists |journal=BMJ |volume=338 |issue= |pages=b220 |year=2009 |pmid=19158173 |doi= |url=http://bmj.com/cgi/pmidlookup?view=long&pmid=19158173}}</ref>
Surgeons know that checklists work and that they save lives.<ref name=pmid19158173>{{cite journal |author=Soar J, Peyton J, Leonard M, Pullyblank AM |title=Surgical safety checklists |journal=BMJ |volume=338 |issue= |pages=b220 |year=2009 |pmid=19158173 |doi= |url=http://bmj.com/cgi/pmidlookup?view=long&pmid=19158173}}</ref>
Airline pilots have been using checklists for years and years.
Pilots have been using checklists since the 1930s.
 
An excellent book about checklists is: ''The checklist manifesto'' by Harvard surgeon Dr. Atul Gawande.<ref>Gawande A. The checklist manifesto: How to get things right. Metropolitan Books. 2009. URL: [http://www.amazon.com/dp/0805091742 http://www.amazon.com/dp/0805091742]. ISBN-13 978-0805091748.</ref>


===Standard diagnostic notation===
===Standard diagnostic notation===
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Gallbladder, cholecystectomy:<br>
Gallbladder, cholecystectomy:<br>
- Acute cholecystitis.
- Acute cholecystitis.
==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>
*Recut = cut off the top of the block.
*Serial sections = make several cuts off the top of the block and look at all of 'em.
*Level = trim the block ~30 micrometres --throw away trimmed tissue-- and then cut a section to look at.
*Deeper = trim the block ~100 micrometres --throw away trimmed tissue-- and then cut a section to look at.
==See also==
*[[Granulation tissue]].
*[[No truth in names]].
*[[Blood work]].
*[[Quality]].


==References==
==References==
Michael
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