Difference between revisions of "Basics"

*Too much '''PINK''' = DEAD ([[necrosis]]).

*''Blue is bad and pink is dead!''<ref>Streutker, C. 8 June 2013.</ref>

*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.

 

#*Most other things.

===Staining===

*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>

**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.

*[http://en.wikipedia.org/wiki/File:Nuclear_changes.jpg Karyolysis, pyknosis, karyorrhexis (WP)].

 

 

 

*[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==

===Features of malignancy===

 

 

 

 

 

{{familytree | B11 | | | | B12 |B11=Primary|B12=[[metastasis|Metastatic]] }}

 

===A general clinico-histomorphologically motivated differential diagnosis of malignancy===

DDX OF MALIGNANCY - THE NEXT STEP

{{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]]}}

*''[[Malignant melanoma]]'', also ''melanoma'', is a separate category as it can look like almost anything under the microscope.

*''Hematologic'' includes [[lymphoma]], [[leukemia]], [[plasma cell neoplasms]] and others.

Memory device ''HMN GEM'': hematologic, melanoma, neuroendocrine carcinoma, germ cell, epithelial, mesenchymal.

====Morphologic categorization====

=====Factors to consider=====

#*Large [[nucleoli]] (nucleoli seen with the 10x objective) pretty much exclude neuroendocrine.

| 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>

| 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 †

|-

| Small lymphoid ([[small cell lymphoma]]).

| 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

 

*† 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 versus cohesive======

{| class="wikitable sortable"

| equal spacing ''or'' 3-D clusters ''or'' intracellular bridges

| visible & opposed (in >50% of cells)

| unequal spacing, thin space surrounds cell

| Value/utility

| equal or 3-D clusters suggests cohesive, pericellular space/rim suggests dyscohesive

Strong predictors of ''cohesive'':

*Intracellular bridges.

 

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.

 

*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'', site (location) very useful - esp. gonadal, midline, retroperitoneal.

*[[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.

 

{{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 | |,|-|-|-|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]]}}

 

 

 

The ''[[long power list]]'' is a longer list for the common sites.

===Lymph node metastasis===

*Lymph node metastasis are usually obvious.

**There are of course exceptions, e.g. [[small cell carcinoma]], [[invasive lobular carcinoma]].

*Histiocytes may be difficult to separate from tumour - especially for the novice.

**Histiocytes may be 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]]''.

===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:

*Cells typically 2-3x the size of a lymphocyte.

*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.

====Images====

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)

*[http://www.engravingarts.com/sales/LVX2.jpg Signet rings (engravingarts.com)].

===Necrosis===

*Dead cells - pink (on H&E).

**Anucleate cells ("Ghost cells")/outlines of cells - usu. subtle.

*+/-Neutrophils (very common).

DDx of necrosis:

*Fibrin.

*[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>

Image:Systemic_lupus_erythematosus_lymphadenopathy_-_high_mag.jpg | Necrosis in [[SLE lymphadenopathy]]. (WC/Nephron)

==Granulomas==

{{Main|Granuloma}}

===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).

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)

====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).

*Schwann cells (found in nerve): nuclei = wavy appearance, thin. (???)

===Pigmented material===

*[[AKA]] brown/black granular crap.

DDx of granular stuff/pigment:

#Foreign material (tattoo pigment, anthracotic pigment, [[amalgam tattoo]]).

Notes:

====[[Stains]] that can help sort it out====

*Prussian blue (iron stain) for hemosiderin.

*[[Fontana-Masson stain]] (or ''Melan A'') for melanin.

*[[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.

 

 

*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.

==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>

==Pathology & pathologists==

===[[Fixation]] & lifestyle===

**"HPF" has no agreed upon definition and, IMHO, should '''''never''''' be used without a non-ambiguous definition.

{{Main|Pathology reports}}

The key point in report writing is that the report should be precise, complete and easy-to-understand.  

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.

Pathologists will probably use more checklists in the future... they are deemed effective in a number of places inside and outside of medicine.

Pilots have been using checklists since the 1930s.