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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.
Line 19: Line 31:
**''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.
 
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>


==DDx in medicine==
==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.
 
======Types of cells======
{| class="wikitable sortable"
! Type
! Morphology
! Significance
|-
| [[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
|}


Probable category by morphology:
Note:
*Carcinoma = cohesive, relatively large (>~2X neutrophil), +/-nucleolus, +/-gland formation (circular structures), often moderate to abundant cytoplasm.
*† Diameter of a "resting lymphocyte" ~ diameter of a [[red blood cell]] (RBC) ~ 8 micrometres.
*Sarcoma = cohesive, composed of spindle cells (cells taper at both ends, nucleus oval/cigar-shaped).
**Most carcinoma cells are 3-4x the size of a RBC.
*Germ cell tumour = appearance often similar to ''carcinoma''.
*Neuroendocrine carcinoma = cohesive, fine granular chromatin and no nucleolus.
*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.


====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==
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*Nucleus darker (hyperchromatic) - '''key feature'''.
*Nucleus darker (hyperchromatic) - '''key feature'''.
*No nuclear membrane - '''key feature'''.
*No nuclear membrane - '''key feature'''.
*In prophase chromatin may have a scalloped border/beaded border.<ref>URL: [http://www.microbehunter.com/wp/wp-content/uploads/2009/lily_prophase.jpg http://www.microbehunter.com/wp/wp-content/uploads/2009/lily_prophase.jpg] and [http://www.microbehunter.com/2009/12/06/mitosis-stages-of-the-lily/ http://www.microbehunter.com/2009/12/06/mitosis-stages-of-the-lily/]. Accessed on: 3 November 2010.</ref>


DDx:  
DDx:  
*Apoptotic cell -- has nuclear condensation (pyknosis), eosinophilic cytoplasm.
*Apoptotic cell -- has nuclear condensation (pyknosis), eosinophilic cytoplasm.
====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://www.flickr.com/photos/euthman/426956752/ Starburst mitosis (flicker.com)].
====Phases of mitosis====
*Prophase - chromatin condenses to chromosomes.
*Metaphase - chromosome aligned.
*Anaphase - spindles separated.
*Telophase - reversal of prophase.


===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 161: 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 cell carcinoma===
{{Main|Signet ring cell carcinoma}}
*It has been said that there are two types of pathologists... those that have missed SRCs ''and'' those that will miss SRCs.
Microscopic:
*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.
*Often have a crescent-shaped ''or'' ovoid nucleus.
**Capillaries sectioned on their lumen have endothelial cells -- the nuclei of these are more spindled.
*SRCs are usually close to friend -- another SRC.
**This helps differentiate SRCs from capillaries sectioned on their lumen.
*The mucin is often clear on H&E... but maybe eosinophilic.
DDx:
*[[Fat atrophy]].
Stains:
*PAS stain.
*Alican blue-PAS stain.
====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)].
===Necrosis===
{{Main|Necrosis}}
Features:
*Dead cells - pink (on H&E).
**Anucleate cells ("Ghost cells")/outlines of cells - usu. subtle.
***Fluffy appearance.
*+/-Neutrophils (very common).
DDx of necrosis:
*Fibrin.
Images (necrosis):
*[http://www0.sun.ac.za/ortho/webct-ortho/tb/tb-histology.html Necrosis at the centre of a granuloma (sun.ac.za)].
*[http://www.biomedical-engineering-online.com/content/9/1/10/figure/F7?highres=y Necrosis (biomedical-engineering-online.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>
<gallery>
Image:Cat_scratch_disease_-_very_high_mag.jpg | Necrosis in [[cat scratch disease]]. (WC/Nephron)
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==
{{Main|Granuloma}}
==Common morphologic problems==
===DDx of pink stuff (on H&E)===
===DDx of pink stuff (on H&E)===
The ''ABCs'' of pink:
The ''ABCs'' of pink:
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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====
Line 196: Line 446:
*Schwann cells (found in nerve): nuclei = wavy appearance, thin. (???)
*Schwann cells (found in nerve): nuclei = wavy appearance, thin. (???)


===Signet ring cells===
===Pigmented material===
Definition:
*[[AKA]] brown/black granular crap.
*Signet ring cells resemble [http://www.engravingarts.com/sales/LVX2.jpg signet rings (image)].
**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:
*Typically 2-3x the size of a lymphocyte.
**Smaller than the typical adipocyte.
*Often have a [http://en.wikipedia.org/wiki/File:Crescent.svg cresentic-shaped] nucleus, or ovoid nucleus.
**Capillaries sectioned on their lumen have endothelial cells-- the nuclei of these are more spindled.
*SRCs are usually close to friend (another SRC)
**This helps differentiate SRCs from capillaries sectioned on their lumen.
*The mucin is often clear on H&E... but maybe eosinophilic.
 
Stains:
*PAS stain.
*Alican blue-PAS stain.
 
Images:
*[http://commons.wikimedia.org/wiki/File:Signet_ring_cells_5.jpg SRCs (H&E) by Nephron] - wikimedia.org.
*[http://commons.wikimedia.org/wiki/File:Gastric_signet_ring_cell_carcinoma_histopatholgy_(2)_PAS_stain.jpg SRC AL-PAS stain] - wikimedia.org.
*[http://commons.wikimedia.org/wiki/File:Gastric_signet_ring_cell_carcinoma_histopatholgy_(1).jpg SRC H&E stain] - wikimedia.org.
 
Comment:
It has been said that there are two types of pathologists... those that have missed SRCs ''and'' those that will miss SRCs.
 
==Granulomas==
*Granulomas can be elusive to the novice.
*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===
Broadly they can be divided (histologically) into:
*Necrosing (also ''caseating'').
**More likely to be infectious.
**Examples: Tuberculosis.
*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 of granulomas:
#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.


===Lung granulomata===
DDx of granular stuff/pigment:
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.
 
==Granular crap DDx==
DDx of granular stuff:
#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.


Note:
Notes:
*Granular stuff should prompt consideration of ''malignant melanoma''.
*Granular stuff should prompt consideration of ''malignant melanoma''.
*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.
 
==Malignancy & inflammation==
If there is lots of inflammation... and you're thinking cancer you should probably back-off, i.e. tend toward benign.  Inflammation can make cells look more malignant than they might be if left alone.
 
==Infectious stuffs==
Images: [http://www.uphs.upenn.edu/bugdrug/antibiotic_manual/Gram3.htm http://www.uphs.upenn.edu/bugdrug/antibiotic_manual/Gram3.htm]
 
*Staphylococcus - in clusters.
*Streptococcus - in chains.


==Staining==
==Staining==
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==Immunohistochemistry==
==Immunohistochemistry==
{{main|Immunohistochemistry}}
{{main|Immunohistochemistry}}
If the special stains don't help... there is immunohistochemistry.


==Food and pathology==
==Food and pathology==
{{main|Pathology and food}}
{{main|Pathology and food}}


==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 353: Line 505:
*ECOG 5: dead.
*ECOG 5: dead.


==Fixation & lifestyle==
==Pathology & pathologists==
===[[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>
===Malignancy & inflammation===
If there is lots of inflammation... and you're thinking cancer you should probably back-off, i.e. tend toward benign.  Inflammation can make cells look more malignant than they might be if left alone.
==Miscellaneous==
===Infectious stuffs===
{{main|Microorganisms}}
Images: [http://www.uphs.upenn.edu/bugdrug/antibiotic_manual/Gram3.htm http://www.uphs.upenn.edu/bugdrug/antibiotic_manual/Gram3.htm]
*Staphylococcus - in clusters.
*Streptococcus - in chains.


==Microscopes==
==Microscopes==
{{main|HPFitis}}
*Pathologists throw around the term ''high power field'' (''HPF'').
*Pathologists throw around the term ''high power field'' (''HPF'').
**"HPF" has no agreed upon definition and, IMHO, should '''''never''''' be used without definition.
**"HPF" has no agreed upon definition and, IMHO, should '''''never''''' be used without a non-ambiguous definition.


''HPF'' generally refers to the area seen with the largest magnification objective (40x), i.e. the field at 400x (as the eye piece magnification is usually 10x).  The field size varies significantly from microscope to microscope.
''HPF'' generally refers to the area seen with the largest magnification objective (40x), i.e. the field at 400x (as the eye piece magnification is usually 10x).  The field size varies significantly from microscope to microscope.
Line 377: 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 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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