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This article serves as an '''introduction''' to [[anatomical pathology]] and discusses the '''basics'''.
==Pathology simplified==
H&E is the standard...
*Too much '''PINK''' = DEAD (necrosis).
*Too much '''BLUE''' = BAD.
In words:
*''Blue is bad and pink is dead!''<ref>Often said by STC.</ref>
Note:
*Lymph nodes are very blue... they aren't necessarily bad.
==Terms==
===Very common===
*Eosinophilic - pink.
*Hyperchromatic - blue.
*Amphophilic - ''bluish-red'' colour when referring to H&E stained section.<ref>URL:[http://pancreaticcancer2000.com/page1.htm http://pancreaticcancer2000.com/page1.htm]. Accessed on: 3 June 2010.</ref>
**''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)].
===Less common===
*Hobnail - basement membrane area < area exposed to luminal surface.
*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>
**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===
There are several fancy terms:<ref>[http://upload.wikimedia.org/wikipedia/en/5/51/Nuclear_changes.jpg http://upload.wikimedia.org/wikipedia/en/5/51/Nuclear_changes.jpg]</ref>
*Karyolysis = nuclear fading/dissolution.
*Pyknosis = nuclear shrinkage.
*Karyorrhexis = nuclear fragmentation.
Image:
*[http://upload.wikimedia.org/wikipedia/en/5/51/Nuclear_changes.jpg Karyolysis, pyknosis, karyorrhexis (wikimedia.org)].
==DDx in medicine==
Mnemonic ''CINE-TV-DATE'':
*Congenital.
*Inflammatory.
*Neoplastic.
*Endocrine.
*Trauma.
*Vascular.
*Degenerative.
*Autoimmune.
*Toxic.
*Everything else (iatrogenic, idiopathic, psychiatric).
In diagnostic pathology, most stuff falls into the ''neoplastic'' category.
===Basic pathologic [[DDx]] of malignancy===
<!--
DDX OF MALIGNANCY
-->
{{familytree/start}}
{{familytree | | | | | | | | | | | A | | | | | | | | | | |A=Malignancy}}
{{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/end}}
Notes:
*''Melanoma'', i.e. ''malignant melanoma'', is a separate category as it can look like almost anything under the microscope.
*''Lymphoma'' includes leukemia.
===Morphologic grouping===
Factors to consider when attempting to group by morphology:
#Cell cohesion - dyscohesive vs. cohesive.
#*If one sees several groups of 5+ cells... probably cohesive.
#*Presence of cell cohesion strongly disfavours lymphoma.
#Cell size - in relation to a neutrophil or red blood cell.
#Cytoplasm - abundance (scant, moderate, abundant).
#*Eosinophilic cytoplasm disfavours lymphoma.
#Chromatin - coarseness (fine, granular).
#Nucleoli - number (absent, present, multiple).
#*Large nucleoli (nucleoli seen with the 10x objective) pretty much exclude neuroendocrine.
Probable category by morphology:
*Carcinoma = cohesive, relatively large (>~2X neutrophil), +/-nucleolus, +/-gland formation (circular structures), often moderate to abundant cytoplasm.
*Sarcoma = cohesive, composed of spindle cells (cells taper at both ends, nucleus oval/cigar-shaped).
*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====
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"
!|
!| Cell spacing
!| Cell membrane
!| Cytoplasm, abundance
!| Cytoplasm, staining
|-
| '''Cohesive'''
| equal spacing ''or'' 3-D clusters ''or'' intracellular bridges
| visible & opposed (in >50% of cells)
| scant to abundant
| any
|-
| '''Dyscohesive'''
| unequal spacing, thin space surrounds cell
| not apparent
| usually scant
| usually basophilic
|-
| Value/utility
| equal or 3-D clusters suggests cohesive, pericellular space/rim suggests dyscohesive
| visible opposed membrane r/i cohesive
| abundant usu. cohesive
| eosinophilic usu. cohesive
|}
Strong predictors of ''cohesive'':
*Intracellular bridges.
*3-D clusters.
*Nuclear moulding.
Weak predictors of ''cohesive'':
*Eosinophilic cytoplasm.
*Abundant cytoplasm.
*>2 X RBC diameter (most lymphoma smaller).
Weak predictors of ''dyscohesive'':
*Pericellular space/rim.
*Scant cytoplasm.
*Basophilic cytoplasm.
===Histomorphologic classification===
Types of 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>
**Suggests mesenchyme, i.e. sarcoma, compatible with melanoma and some carcinomas.
*Plasmacytoid cell.
**Resemble a plasma cell: eccentric nucleus, "clockface" chromatin pattern, scant basophilic cytoplasm.
*Epithelioid cell.
**Looks like epithelium - cell borders touch neighbouring cells so that the cells collectively form a barrier.
*[[Small round blue cell tumour]]:
**Small cells with scant cytoplasm.
==Finding the elements==
===Mitoses===
*Nucleus darker (hyperchromatic) - '''key feature'''.
*No nuclear membrane - '''key feature'''.
DDx:
*Apoptotic cell -- has nuclear condensation (pyknosis), eosinophilic cytoplasm.
===Neutrophils===
*Little dots = the multilobular nucleus - '''key feature'''.
*Neutrophils are often found with friends, i.e. lymphocytes, plasma cells.
DDx of little specs:
*Nuclear debris - apoptotic cell.
**Apoptotic cell -- has nuclear condensation (pyknosis), eosinophilic cytoplasm.
Notes:
*AKA '''PMNs''' - polymorphonuclearcyte, polymorphonuclear cell.
*You find PMNs by their nucleus; on a histologic section don't bother looking for the cell membrane (they are usually impossible to see).
*A collection of PMNs... think about ''necrosis'' and ''abscess''.
===Lymph node metstatsis===
*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.
*Subcapsular space - the first place to look for mets.
*Lymph node metstasis are usually obvious.
*Histiocytes may be difficult to separate from tumour - esp. initially.
**Histiocytes usually are in germinal centre, i.e. the node architecture helps,
**Malignant cells have to have malignant features, i.e. the NC ratio is abnormal, there is nuclear pleomorphism.
See: ''[[Lymph node]]'' article for a detailed description of cell types in a lymph node.
===DDx of pink stuff (on H&E)===
The ''ABCs'' of pink:
*'''A'''myloid.
*'''B'''lood clot (organized); fibrin.
*'''C'''ollagen (fibrous tissue).
*'''S'''mooth muscle cells (SMCs).
====Smooth muscle cells (SMCs) vs. fibrous tissue====
Fibroblasts (fibrous tissue):
*Wavy nuclei with pointy ends.
*Less nuclei.
SMCs:
*Elliptical nuclei.
*More nuclei.
Remembering the above:
*SMCs are stretched; ergo, not wavy.
*Fibrous tissue is fibrous... more protein... less cells; ergo, less nuclei.
*'''F'''ibroblast = '''f'''ootball-like.
*Cigar-shaped nuclei (SMCs) are affected by cigars (smoking causes vascular disease).
Notes:
*Schwann cells (found in nerve): nuclei = wavy appearance, thin. (???)
===Signet ring cells===
Definition:
*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===
====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.
==Granular crap DDx==
==Granular crap DDx==
DDx of granular stuff:
DDx of granular stuff:
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#Melanin.
#Melanin.


Note:
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.


Stains that can help sort it out:
===[[Stains]] that can help sort it out===
*Prussian blue for hemosiderin.
*Prussian blue for hemosiderin.
*Melan A for melanin.
*Melan A for melanin.
*Kluver-Barrera for lipofuscin.
*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==
{{main|Stains}}
Basic knowledge of stain is important.  The above article starts with H&E and goes from there.
==Immunohistochemistry==
{{main|Immunohistochemistry}}
==Food and pathology==
{{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.
==Oncologist talk==
*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 score:
*ECOG 0: healthy.
*ECOG 1: ambulatory, no strenuous activity.
*ECOG 2: limited to self-care in bed <50% of time.
*ECOG 3: difficult to care for self in bed >50% of time.
*ECOG 4: bed bound.
*ECOG 5: dead.
==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>
==Microscopes==
{{main|HPFitis}}
*Pathologists throw around the term ''high power field'' (''HPF'').
**"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.
===Estimating ''field of view''===
FOV = D<sub>eye piece</sub> x 1/M<sub>obj</sub>.
Where:
*FOV = field of view.
*D<sub>eye piece</sub> = diameter of eye piece (this is usually inscribed on the side of the eye piece).
*M<sub>obj</sub> = magnification of the objective.
Example:
*D<sub>eye piece</sub> = 22 mm
*M<sub>obj</sub> = 40x (largest magnification objective)
Applying the formula:
*FOV = 22 mm / 40
*FOV = 0.55 mm
==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.
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===
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>
====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].
I suspect pathologists will 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>
Airline pilots have been using checklists for years and years.
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===
Site, operation/procedure:<br>
- Tissue type diagnosis.
Example:
<br>
Gallbladder, cholecystectomy:<br>
- Acute cholecystitis.
==References==
{{reflist|2}}
==External links==
*[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] - cap.org.
*[http://focosi.altervista.org/pathohomoprocess_regressive.html Regressive histopathologic findings (altervista.org)].
*[http://granuloma.homestead.com/ Atlas of Granulomatous Diseases (granuloma.homestead.com)].
[[Category:Basics]]
Michael
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