Difference between revisions of "Esophagus"

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Esophagus (view source)

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'''Esophagus''' connects the pharynx to the [[stomach]].  It is afflicted by tumours on occasion. For some reason or another, it seems everyone at SMH gets a esophageal biopsy... yet patients at SB don't have esophagi.
[[Image:Tractus intestinalis esophagus.svg|thumb|250px|A schematic of the esophagus.]]
'''Esophagus''' connects the pharynx to the [[stomach]].  It is afflicted by tumours on occasion. Probably the most common affliction is [[gastroesophageal reflux disease]] (GERD). Most biopsies revolve around the questions: 1. intestinal metaplasia? 2. dysplasia? and 3. cancer?


=Normal=
=Normal esophagus=
General:
General:
*Stratified squamous non-keratinized epithelium.
*Stratified squamous non-keratinized epithelium.
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**Mitoses should be rare and should NOT be above the basal layer.
**Mitoses should be rare and should NOT be above the basal layer.
*Inflammatory cells should be very rare.
*Inflammatory cells should be very rare.
==Sign out==
===Nonspecific inflammation===
<pre>
Esophagus, Distal, Biopsy:
- Columnar epithelium with moderate chronic inflammation.
- Reactive squamous epithelium.
- NEGATIVE for intestinal metaplasia.
- NEGATIVE for dysplasia and NEGATIVE for malignancy.
</pre>
====Block letters====
<pre>
ESOPHAGUS, DISTAL, BIOPSY:
- COLUMNAR EPITHELIUM WITH MODERATE CHRONIC INFLAMMATION.
- REACTIVE SQUAMOUS EPITHELIUM.
- NEGATIVE FOR INTESTINAL METAPLASIA.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.
</pre>


=Diagnoses=
=Diagnoses=
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| -
| -
| -
| -
| [http://commons.wikimedia.org/wiki/File:Tinci%C3%B3n_hematoxilina-eosina.jpg]
| [[Image:Tinci%C3%B3n_hematoxilina-eosina.jpg|center|thumb|125px|Normal esophagus. (WC)]]
|-  
|-  
|GERD
|GERD
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|
|
| incr. risk of Barrett's
| incr. risk of Barrett's
|
| [[Image:Gastroesophageal reflux disease -- low mag.jpg|center|thumb|125px|c/w GERD. (WC)]]
|-  
|-  
|Eosinophilic esophagitis
|[[Eosinophilic esophagitis]]
| abundant eosinophils
| abundant eosinophils
| elongated (epithelial) papillae, basal cell hyperplasia, lymphocytes
| elongated (epithelial) papillae, basal cell hyperplasia, lymphocytes
|
|
| unresponsive to PPIs
| unresponsive to PPIs
| [http://en.wikipedia.org/wiki/File:Eosinophilic_esophagiits_path.jpg microscopic], [http://en.wikipedia.org/wiki/File:Eosinophilic_esophagiits_path.jpg endoscopic]
| [[Image:Eosinophilic_esophagitis_-_2_-_very_high_mag.jpg|center|thumb|125px|Eosinophilic esophagitis. (WC/Nephron)]]
|-  
|-  
|Barrett's type change
|[[Barrett's esophagus|Barrett's type change]]
| goblet cells
| goblet cells
| no dysplasia
| no dysplasia
| Alcian blue +ve
| Alcian blue +ve
| incr. risk of adenocarcinoma
| incr. risk of adenocarcinoma
| [http://commons.wikimedia.org/wiki/File:Barretts_alcian_blue.jpg]
| [[Image:Barretts_alcian_blue.jpg|center|thumb|125px|Barrett's esophagus. Alcian blue. (WC)]]
|-  
|-  
|Dysplasia, low grade
|[[Columnar dysplasia of the esophagus|Dysplasia, low grade]]
| nuclear crowding at surface
| nuclear crowding at surface
| hyperchromasia, mild arch. complexity, no necrosis
| hyperchromasia, mild arch. complexity, no necrosis
|
|
| incr. risk of carcinoma
| incr. risk of carcinoma
|
| [[Image:Low-grade columnar dysplasia of the esophagus -- intermed mag.jpg|thumb|110px|LGH - intermed. mag.]]
|-  
|-  
|Dysplasia, high grade
| [[Columnar dysplasia of the esophagus|Dysplasia, high grade]]
| cribriforming and/or necrosis  
| [[cribriform]]ing and/or necrosis  
| nuclei often round & large, hyperchromasia
| nuclei often round & large, hyperchromasia
|
|
| marked incr. risk of carcinoma
| marked incr. risk of carcinoma
|
| [[Image:High-grade columnar dysplasia of the esophagus -- high mag.jpg|thumb|110px|HGD - high mag.]]
<!--
<!--
|Entity
|Entity
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|-  
|-  
|Normal  
|Normal  
| matures
| '''matures'''
| round glands
| round glands
| no nuclear atypia
| no nuclear atypia
| -
| -
| -
| -
| Image
| [[Image:Tinci%C3%B3n_hematoxilina-eosina.jpg|center|thumb|125px|Normal esophagus. (WC)]]
|-  
|-  
|Barrett's eosphagus  
|Barrett's esophagus  
| matures
| matures
| round glands, normal gland density
| round glands, normal gland density
| +/-scant nuclear atypia
| +/-scant nuclear atypia
| goblet cells
| '''goblet cells'''
| clinical diagnosis
| clinical diagnosis
| Image
| Image
|-  
|-  
|Indefinite for columnar dysplasia  
|Indefinite for columnar dysplasia  
| moderate-to-minimal maturation
| minimal maturation ''or'' '''cannot see surface'''
| round glands, normal gland density
| round glands, normal gland density
| mild nuclear atypia, nuclear pseudostratification, no necrosis
| mild nuclear atypia, '''nuclear pseudostratification''', no necrosis
| -
| -
| follow-up
| follow-up
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| minimal-to-scant maturation
| minimal-to-scant maturation
| round glands, +/-rare budding, increased gland density
| round glands, +/-rare budding, increased gland density
| mild-to-moderate nuclear atypia, nuclear pseudostratification, no necrosis
| mild-to-moderate nuclear atypia, '''nuclear pseudostratification''', '''no necrosis'''
| -
| -
| follow-up
| follow-up
| Image
| [[Image:Low-grade columnar dysplasia of the esophagus -- intermed mag.jpg|thumb|110px|LGH - intermed. mag.]]
|-  
|-  
|High-grade columnar dysplasia  
|High-grade columnar dysplasia  
| no maturation
| no maturation
| incr. density of irregular glands with budding and/or rare cribriforming and/or gland dilation
| '''incr. density of irregular glands''' with budding and/or rare cribriforming and/or gland dilation
| moderate-to-marked nuclear atypia (usu. plump round nuclei), hyperchromasia, +/-necrosis
| moderate-to-marked nuclear atypia (usu. plump round nuclei), hyperchromasia, +/-necrosis
| -
| -
| EMR, surgery
| [[EMR]], surgery
| Image
| [[Image:High-grade columnar dysplasia of the esophagus -- high mag.jpg|thumb|110px|HGD - high mag.]]
|-  
|-  
|Intramucosal adenocarcinoma  
|Intramucosal adenocarcinoma  
| no maturation
| no maturation
| single cells or back-to-back irregular glands with budding and/or cribriforming and/or gland dilation or glands with long axis along muscularis mucosae
| single cells or '''back-to-back irregular glands''' with budding and/or '''[[cribriform]]ing''' and/or '''gland dilation''' or glands with long axis along muscularis mucosae
| moderate-to-marked nuclear atypia - usu. round large nuclei, hyperchromasia, +/-necrosis
| moderate-to-marked nuclear atypia - usu. round large nuclei, hyperchromasia, +/-necrosis
| -
| -
| EMR, surgery
| [[EMR]], surgery
| Image
| [[Image:Esophageal_adenocarcinoma_-_high_mag.jpg|thumb|110px|Adenocarcinoma - high mag.]]
|}
|}


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| low vs. high
| low vs. high
|-
|-
| Desmoplasia
| [[Desmoplasia]]
| absent
| absent
| absent
| absent
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|-
|-
|}
|}
====Decision tree for columnar dysplasia====
Odze has made an algorithm - see: [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1861756/figure/fig8/ Diagnostic algorithm (nih.gov)].<ref name=pmid17021130>{{Cite journal  | last1 = Odze | first1 = RD. | title = Diagnosis and grading of dysplasia in Barrett's oesophagus. | journal = J Clin Pathol | volume = 59 | issue = 10 | pages = 1029-38 | month = Oct | year = 2006 | doi = 10.1136/jcp.2005.035337 | PMID = 17021130 }}</ref>


==Indications==
==Indications==
*Pyrosis = heartburn.<ref>URL: [http://dictionary.reference.com/browse/pyrosis http://dictionary.reference.com/browse/pyrosis]. Accessed on: 21 June 2010.</ref>
*Pyrosis = heartburn.<ref>URL: [http://dictionary.reference.com/browse/pyrosis http://dictionary.reference.com/browse/pyrosis]. Accessed on: 21 June 2010.</ref>


=Infection=
=Infectious esophagitis=
{{main|Microorganisms}}
{{main|Microorganisms}}
Is a relatively common problem, especially in those that live at the margins (EtOH abusers) and immunosuppressed individuals ([[HIV|HIV/AIDS]]).
Is a relatively common problem, especially in those that live at the margins (EtOH abusers) and immunosuppressed individuals ([[HIV|HIV/AIDS]]).
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*[[HIV]] - non-specific.
*[[HIV]] - non-specific.


===Candidiasis===
===Candida esophagitis===
{{Main|Candidiasis}}
*[[AKA]] ''esophageal candidiasis''.
 
====Gross (endoscopic)====
====Gross (endoscopic)====
Features:
Features:
*White patches.
*White patches.
DDx (endoscopic):<ref name=Ref_Odze244>{{Ref Odze|244}}</ref>
*[[Eosinophilic esophagitis]].


====Microscopic====
====Microscopic====
Features:
Features:
*Worm-like micro-organisms.
*Worm-like micro-organisms - '''key feature'''.
**Pseudohyphae (single cells).
**Pseudohyphae (single cells).
**Thickness ~ 1/3-1/2 of squamous cell nucleus.
**Thickness ~ 1/3-1/2 of squamous cell nucleus.
**Should be within (squamous) epithelium.
**Should be within (squamous) epithelium.
***On top of epithelium does not count,<ref>ALS. 4 October 2010.</ref> i.e. it is likely an artifact.  
*Superficial inflammation - esp. [[neutrophils]] - '''important'''.
 
Notes:
*On top of epithelium does not count,<ref>ALS. 4 October 2010.</ref> i.e. it is likely an artifact.  
*Bacilli and cocci may accompany the candida. They are typically ignored.
 
DDx:
*[[Acute esophagitis]] - no candida seen.
 
=====Image=====
<gallery>
Image:Esophageal_candidiasis_(2)_PAS_stain.jpg | Esophageal candidiasis. (WC)
</gallery>
 
====Sign out====
<pre>
ESOPHAGUS, BIOPSY:
- ESOPHAGITIS WITH FUNGAL ORGANISMS CONSISTENT WITH CANDIDA.
</pre>


Image: [http://en.wikipedia.org/wiki/File:Esophageal_candidiasis_(2)_PAS_stain.jpg Esophageal candidiasis (WC)].
<pre>
ESOPHAGUS, BIOPSY:
- ACUTE ESOPHAGITIS WITH FUNGAL ORGANISMS CONSISTENT WITH CANDIDA.
- NEGATIVE FOR INTESTINAL METAPLASIA.
- NEGATIVE FOR DYSPLASIA.
</pre>


===Cytomegalovirus esophagitis===
===Cytomegalovirus esophagitis===
*[[AKA]] [[CMV]] esophagitis.
*[[AKA]] [[CMV]] esophagitis.


Microscopic:
====Microscopic====
Features:
*Classically at the base of the ulcer; within endothelial cells - '''key point'''.
*Classically at the base of the ulcer; within endothelial cells - '''key point'''.


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===Herpes esophagitis===
===Herpes esophagitis===
====General====
{{Main|Herpes esophagitis}}
Etiology:
*[[Herpes simplex virus]].
 
====Microscopic====
Features (3 Ms):
*'''M'''oulding.
*'''M'''ultinucleation.
*'''M'''argination of chromatin.
 
Images:
*[http://commons.wikimedia.org/wiki/File:Herpes_esophagitis_-_very_high_mag.jpg HSV esophagitis - very high mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Herpes_esophagitis_-_intermed_mag.jpg HSV esophagitis - intermed. mag. (WC)].


===Human papillomavirus esophagitis===
===Human papillomavirus esophagitis===
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*[http://commons.wikimedia.org/wiki/File:Low-grade_sil_and_endocx.jpg LSIL & endocervix (WC)].
*[http://commons.wikimedia.org/wiki/File:Low-grade_sil_and_endocx.jpg LSIL & endocervix (WC)].


=Other=
=Non-neoplastic disease=
The group of conditions doesn't fit neatly with the others.  It is a mixture of different non-neoplastic conditions.
==Gastroesophageal reflux disease==
==Gastroesophageal reflux disease==
===General===
*Abbreviated ''GERD'' or ''GORD'' (gastro-oesophageal reflux disease).
*Abbreviated ''GERD'' and ''GORD'' (gastro-oesophageal reflux disease).
*[[AKA]] ''reflux esophagitis''.
 
{{Main|Gastroesophageal reflux disease}}
Clinical:
*Treated with proton pump inhibitors (PPIs).
 
===Microscopic===
Features:
#Basal cell hyperplasia;<ref name=pmid16707971>{{Cite journal  | last1 = Steiner | first1 = SJ. | last2 = Kernek | first2 = KM. | last3 = Fitzgerald | first3 = JF. | title = Severity of basal cell hyperplasia differs in reflux versus eosinophilic esophagitis. | journal = J Pediatr Gastroenterol Nutr | volume = 42 | issue = 5 | pages = 506-9 | month = May | year = 2006 | doi = 10.1097/01.mpg.0000221906.06899.1b | PMID = 16707971 }}</ref> > 3 cells thick ''or'' >15% of epithelial thickness.
#Papillae elongated; papillae reach into the top 1/3 of the epithelial layer.<ref name=Ref_PBoD804>{{Ref PBoD|804}}</ref>
#Inflammation, esp. eosinophils, lymphocytes with convoluted nuclei ("squiggle cells").
#+/-Spongiosis.
#+/-Apoptotic cells.<ref name=pmid9926792>{{cite journal |author=Wetscher GJ, Schwelberger H, Unger A, ''et al.'' |title=Reflux-induced apoptosis of the esophageal mucosa is inhibited in Barrett's epithelium |journal=Am. J. Surg. |volume=176 |issue=6 |pages=569–73 |year=1998 |month=December |pmid=9926792 |doi= |url=}}</ref>
 
Notes:
*Eosinophilic esophagitis is characterized by similar histomorphologic features -- key difference: more eosinophils.
*"Squiggle cells" may mimic neutrophils.
 
Images:
*[http://www.archivesofpathology.org/action/showFullPopup?id=i1543-2165-134-6-815-f03&doi=10.1043%2F1543-2165-134.6.815 EE versus GERD (archivesofpathology.org)].<ref name=pmid20524860/>


==Eosinophilic esophagitis==
==Eosinophilic esophagitis==
===General===
*Abbreviated ''EE''.
*The current thinking is that it is a clinico-pathologic diagnosis.<ref name=pmid20524860>{{Cite journal  | last1 = Genevay | first1 = M. | last2 = Rubbia-Brandt | first2 = L. | last3 = Rougemont | first3 = AL. | title = Do eosinophil numbers differentiate eosinophilic esophagitis from gastroesophageal reflux disease? | journal = Arch Pathol Lab Med | volume = 134 | issue = 6 | pages = 815-25 | month = Jun | year = 2010 | doi = 10.1043/1543-2165-134.6.815 | PMID = 20524860 | url = http://www.archivesofpathology.org/doi/full/10.1043/1543-2165-134.6.815 }}</ref>
{{Main|Eosinophilic esophagitis}}
 
Clinical:
*Dyspepsia.
**Often mimics gastroesophageal reflux (GERD).<ref name=pmid19596009>{{Cite journal  | last1 = Rothenberg | first1 = ME. | title = Biology and treatment of eosinophilic esophagitis. | journal = Gastroenterology | volume = 137 | issue = 4 | pages = 1238-49 | month = Oct | year = 2009 | doi = 10.1053/j.gastro.2009.07.007 | PMID = 19596009 }}
</ref>
*Dysphagia.<ref>URL: [http://www.medicinenet.com/eosinophilic_esophagitis/page2.htm#tocc http://www.medicinenet.com/eosinophilic_esophagitis/page2.htm#tocc]. Accessed on: 1 December 2009.</ref>
 
Treatment:
*Avoid exacerbating antigens.
*Topical corticosteroids, e.g. fluticasone.
 
Biopsies:
*Should be taken from: upper, mid, lower and submitted in separate containers (eosinophilia present through-out-- to differentiate from GERD).
 
Associations:
*Atopy.<ref name=Ref_GLP19>{{Ref GLP|19}}</ref>
*Celiac disease.<ref name=pmid19841598>{{cite journal |author=Leslie C, Mews C, Charles A, Ravikumara M |title=Celiac disease and eosinophilic esophagitis: a true association |journal=J. Pediatr. Gastroenterol. Nutr. |volume=50 |issue=4 |pages=397–9 |year=2010 |month=April |pmid=19841598 |doi=10.1097/MPG.0b013e3181a70af4 |url=}}</ref>
*Oral antigens, i.e. particular foods.<ref name=pmid19596009/>
*Familial association.<ref name=pmid19596009/>
 
===Gross/endoscopic===
*'''Trachealization'''; eosphagus looks like trachea.<ref name=pmid19636182>{{Cite journal  | last1 = Al-Hussaini | first1 = AA. | last2 = Semaan | first2 = T. | last3 = El Hag | first3 = IA. | title = Esophageal trachealization: a feature of eosinophilic esophagitis. | journal = Saudi J Gastroenterol | volume = 15 | issue = 3 | pages = 193-5 | month =  | year =  | doi = 10.4103/1319-3767.54747 | PMID = 19636182 }}
</ref>
**[[AKA]] Feline Esophagus.<ref>URL: [http://www.ajronline.org/cgi/reprint/164/4/900.pdf  http://www.ajronline.org/cgi/reprint/164/4/900.pdf]. Accessed on: 4 October 2010.</ref>
*White.
 
Image: [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2841420/figure/F0001/ Trachealization - radiograph (nih.gov)].
 
===Microscopic===
Features:<ref name=Ref_GLP19>{{Ref GLP|19}}</ref>
*Mucosa with "abundant eosinophils".
*Basal cell hyperplasia.
**Three cells thick ''or'' >15% of epithelial thickness.
*Papillae elongated.
**Papillae that reach into the top 1/3 of the epithelial layer - definition for GERD.<ref name=Ref_PBoD804>{{Ref PBoD|804}}</ref>
 
Notes "abundant eosinophils":
*Criteria for number of eosinophils/area is '''''highly variable'''''; there is a 23X fold variation in published values and only 11% of studies actually define an area (most studies, embarassing for pathologists that understand this issue, only give the number of eosinophils per "HPF")!<ref name=pmid17617209>{{cite journal |author=Dellon ES, Aderoju A, Woosley JT, Sandler RS, Shaheen NJ |title=Variability in diagnostic criteria for eosinophilic esophagitis: a systematic review |journal=Am. J. Gastroenterol. |volume=102 |issue=10 |pages=2300–13 |year=2007 |month=October |pmid=17617209 |doi=10.1111/j.1572-0241.2007.01396.x |url=}}</ref>
**The group that published the article cited above did another one... <ref name=pmid19830560>PMID 19830560.</ref>
*The most commonly reported cut points are 15, 20 and 24 eosinophils/HPF, without defining HPF.<ref name=pmid17617209/>
**The ''Foundation Series'' book<ref name=Ref_GLP19>{{Ref GLP|19}}</ref> says: "> 20/HPF"; [[VL]] sees this definition as garbage, as "HPF" is not defined (see [[HPFitis]]).
**There is a consensus paper<ref>{{cite journal |author=Furuta GT, Liacouras CA, Collins MH, ''et al.'' |title=Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment |journal=Gastroenterology |volume=133 |issue=4 |pages=1342–63 |year=2007 |month=October |pmid=17919504 |doi=10.1053/j.gastro.2007.08.017 |url=}}</ref> that makes note of [[HPFitis]]... and then goes on to ignore to whole issue by defining EE as 15/HPF.  It blows my mind that the people could be so will fully blind and that the idiotic reviewers didn't understand this.
**Most resident microscopes at the Toronto teaching hospitals have 22 mm eye pieces and have for their highest magnification objective a 40X.  De facto, this means most people in Toronto are using the Liacouras ''et al.'' definition.<ref name=pmid16361045>{{cite journal |author=Liacouras CA, Spergel JM, Ruchelli E, ''et al.'' |title=Eosinophilic esophagitis: a 10-year experience in 381 children |journal=Clin. Gastroenterol. Hepatol. |volume=3 |issue=12 |pages=1198–206 |year=2005 |month=December |pmid=16361045 |doi= |url=}}</ref>
 
Images:
*[http://commons.wikimedia.org/w/index.php?title=File:Eosinophilic_esophagitis_-_2_-_very_high_mag.jpg Eosinophilic esophagitis - very high mag. (WC)].
*[http://commons.wikimedia.org/w/index.php?title=File:Eosinophilic_esophagitis_-_2_-_high_mag.jpg Eosinophilic esophagitis - high mag. (WC)].
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2841420/figure/F0003/ Eosinophilic esophagitis (nih.gov)].
*[http://www.archivesofpathology.org/action/showFullPopup?id=i1543-2165-134-6-815-f03&doi=10.1043%2F1543-2165-134.6.815 EE versus GERD (archivesofpathology.org)].<ref name=pmid20524860/>


==Erosive esophagitis==
==Erosive esophagitis==
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===Pill esophagitis===
===Pill esophagitis===
Classic causes:
Classic causes:
*Alendronate (Fosamax) - for osteoporosis.
*Alendronate (Fosamax) - for [[osteoporosis]].
*Iron (can be demonstrated with Prussian blue stain).
*Iron - can be demonstrated with [[Prussian blue stain]].
*Doxycycline.
*Doxycycline.


=Preneoplastic=
==Esophageal varices==
==Barrett esophagus==
{{Main|Esophageal varices}}
===General===
*Diagnosis is made by '''clinicans ''not'' pathologists'''.
**A common histologic correlate is metaplastic transformation of stratified squamous epithelium to simple columnar epithelium with goblet cells.
***There is disagreement whether goblet cells are required for the diagnosis.<ref name=pmid19623166>{{Cite journal  | last1 = Riddell | first1 = RH. | last2 = Odze | first2 = RD. | title = Definition of Barrett's esophagus: time for a rethink--is intestinal metaplasia dead? | journal = Am J Gastroenterol | volume = 104 | issue = 10 | pages = 2588-94 | month = Oct | year = 2009 | doi = 10.1038/ajg.2009.390 | PMID = 19623166 }}</ref>
****One large study suggests that goblets cells are only absent due to undersampling.<ref name=pmid21959311>{{Cite journal  | last1 = Chandrasoma | first1 = P. | last2 = Wijetunge | first2 = S. | last3 = DeMeester | first3 = S. | last4 = Ma | first4 = Y. | last5 = Hagen | first5 = J. | last6 = Zamis | first6 = L. | last7 = DeMeester | first7 = T. | title = Columnar-lined esophagus without intestinal metaplasia has no proven risk of adenocarcinoma. | journal = Am J Surg Pathol | volume = 36 | issue = 1 | pages = 1-7 | month = Jan | year = 2012 | doi = 10.1097/PAS.0b013e31822a5a2c | PMID = 21959311 }}</ref>
*Associated with chronic reflux - ''see: [[gastroesophageal reflux disease]]''.


Significance of Barrett's esophagus:
==Acute esophagitis==
*Increased risk of adenocarcinoma of the esophagus.
{{Main|Acute esophagitis}}
**Need on-going surveillance, i.e. long term follow-up/repeat esophagogastroduodenoscopy.


===Gross===
==Benign esophageal stricture==
*Red/light brown esophageal mucosa.
{{Main|Esophageal stricture}}
**Normal mucosa = light pink.


Image:
==Esophageal duplication cyst==
*[http://commons.wikimedia.org/wiki/File:Barretts_esophagus.jpg Endoscopic image of BE (WC)].
{{Main|Foregut duplication cyst}}


===Microscopic===
==Zenker's diverticulum==
Features:
{{Main|Zenker's diverticulum}}
*Columnar epithelium.
*[[AKA]] ''cricopharyngeal diverticulum'', ''pharyngoesophageal diverticulum'' and ''hypopharyngeal diverticulum''.
*Goblets cells - '''key feature'''.
*+/-Mild hyperchromasia.
*+/-Reactive squamous epithelium suggestive of reflux.


Images:
==Radiation esophagitis==
*[http://commons.wikimedia.org/wiki/File:Barretts_alcian_blue.jpg Barrett's esophagus - alcian blue (WC)].
{{Main|Radiation esophagitis}}


===Stains===
=Preneoplastic=
*Alcian blue - goblet cells +ve.
==Barrett esophagus==
{{Main|Barrett esophagus}}


=Neoplastic=
=Neoplastic=
==Columnar dysplasia==
==Columnar dysplasia of the esophagus==
*[[AKA]] ''esophageal columnar dysplasia'', abbreviated ''ECD''.<ref name=pmid21809994>{{Cite journal  | last1 = Feng | first1 = W. | last2 = Zhou | first2 = Z. | last3 = Peters | first3 = JH. | last4 = Khoury | first4 = T. | last5 = Zhai | first5 = Q. | last6 = Wei | first6 = Q. | last7 = Truong | first7 = CD. | last8 = Song | first8 = SW. | last9 = Tan | first9 = D. | title = Expression of insulin-like growth factor II mRNA-binding protein 3 in human esophageal adenocarcinoma and its precursor lesions. | journal = Arch Pathol Lab Med | volume = 135 | issue = 8 | pages = 1024-31 | month = Aug | year = 2011 | doi = 10.5858/2009-0617-OAR2 | PMID = 21809994 }}</ref>
*[[AKA]] ''dysplasia in the columnar-lined esophagus''.<ref>{{Cite journal  | last1 = Levine | first1 = DS. | title = Management of dysplasia in the columnar-lined esophagus. | journal = Gastroenterol Clin North Am | volume = 26 | issue = 3 | pages = 613-34 | month = Sep | year = 1997 | doi =  | PMID = 9309409 }}</ref>
* [[AKA]] ''columnar epithelial dysplasia''.<ref name=pmid3825997>{{Cite journal  | last1 = Hamilton | first1 = SR. | last2 = Smith | first2 = RR. | title = The relationship between columnar epithelial dysplasia and invasive adenocarcinoma arising in Barrett's esophagus. | journal = Am J Clin Pathol | volume = 87 | issue = 3 | pages = 301-12 | month = Mar | year = 1987 | doi =  | PMID = 3825997 }}</ref>
{{Main|Columnar dysplasia of the esophagus}}
 
==Squamous dysplasia of the esophagus==
*[[AKA]] ''esophageal squamous dysplasia''.
===General===
===General===
*Precursor of [[esophageal squamous cell carcinoma]].<ref name=pmid11936262>{{Cite journal  | last1 = Dry | first1 = SM. | last2 = Lewin | first2 = KJ. | title = Esophageal squamous dysplasia. | journal = Semin Diagn Pathol | volume = 19 | issue = 1 | pages = 2-11 | month = Feb | year = 2002 | doi =  | PMID = 11936262 }}</ref>
*Common in China.<ref name=pmid11936262/>
*Not very common in North America.


====Classification====
===Microscopic===
*Indefinite for dysplasia.
Features:
**Diagnose used in the context of uncertainty (like ''[[gynecologic cytopathology|ASCUS]]'' and ''[[prostate gland|ASAP]]''); usually used in the context of inflammation.
*Squamous cell nuclear atypia.
*Low grade dysplasia.
*Lack of maturation to the surface.
*High grade dysplasia.


====Management====
Note:
Low grade dysplasia.
*Grading differences between Western pathologists and those of the east.<ref name=pmid11936262/>
*Follow-up.


High grade dysplasia.
DDx:
*Endoscopic mucosal resection.<ref name=pmid19306943>{{cite journal |author=Sampliner RE |title=Endoscopic Therapy for Barrett's Esophagus |journal=Clin. Gastroenterol. Hepatol. |volume= |issue= |pages= |year=2009 |month=March |pmid=19306943 |doi=10.1016/j.cgh.2009.03.011 |url=}}</ref>
*Reactive changes.
*Surgical resection.
*[[Esophageal squamous cell carcinoma]].
 
===Microscopic===
Features to assess:<ref name=Ref_GLP46>{{Ref GLP|46}}</ref>
# Lack of surface maturation.
#*Lack of lighter staining at surface.
#*Nuclear crowding at surface.
#*Nuclei at the surface not smaller.
# Architecture - esp. at low power.
#* Glands not round.
#** Low-grade feature: gland budding.
#** High-grade features: cribriforming, cystic dilation, necrotic debris.
#* Gland density:
#** Increased & round - think low-grade dysplasia.
#** Increased & irregular - think high-grade dysplasia.
# Cytology, esp. at high magnification.
#* Nuclear abnormalities in: size, staining, shape.
#* Loss of "nuclear polarity" = high-grade feature
#** Loss of palisaded appearance, rounding-up of nuclei.
# Inflammation, erosions & ulceration.
#* Marked inflammation should prompt consideration of knocking down the diagnosis one step, i.e. low-grade becomes indefinite ''or'' high-grade becomes low-grade.


Negatives:
====Images====
#No desmoplasia.
A set of cases from Japan:<ref name=pmid23330004>{{Cite journal  | last1 = Terada | first1 = T. | title = A clinicopathologic study of esophageal 860 benign and malignant lesions in 910 cases of consecutive esophageal biopsies. | journal = Int J Clin Exp Pathol | volume = 6 | issue = 2 | pages = 191-8 | month =  | year = 2013 | doi =  | PMID = 23330004 }}</ref>
#*Stromal fibrotic reaction to the tumour.
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544238/figure/fig05/ Mild squamous dysplasia (nih.gov)].
#**Desmoplasia is rare in the superficial esophagus.<ref name=Ref_GLP49>{{Ref GLP|49}}</ref>
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544238/figure/fig06/ Moderate squamous dysplasia (nih.gov)].
#No single cells.
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544238/figure/fig07/ Severe squamous dysplasia (nih.gov)].
#No extensive back-to-back glands.
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544238/figure/fig08/ Carcinoma in situ (nih.gov)].
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544238/figure/fig09/ Squamous cell carcinoma of the esophagus (nih.gov)].


Notes:
===IHC===
*Changes similar to those see in colorectal tubular adenomas; however, what would be low-grade dysplasia in the rectum is high-grade dysplasia in the esophagus.
*Ki-67 may be useful:<ref name=pmid21420715>{{Cite journal  | last1 = Wang | first1 = WC. | last2 = Wu | first2 = TT. | last3 = Chandan | first3 = VS. | last4 = Lohse | first4 = CM. | last5 = Zhang | first5 = L. | title = Ki-67 and ProExC are useful immunohistochemical markers in esophageal squamous intraepithelial neoplasia. | journal = Hum Pathol | volume = 42 | issue = 10 | pages = 1430-7 | month = Oct | year = 2011 | doi = 10.1016/j.humpath.2010.12.009 | PMID = 21420715 }}</ref>
*Presence of goblet cells is mildly reassuring its not dysplasia.<ref>GAG. January 2009.</ref>
**Reactive changes/normal: ~98% negative, ~2% intermediate.
*Desmoplasia present = invasive adenocarcinoma.<ref name=Ref_GLP54>{{Ref GLP|54}}</ref>
**Low-grade esophageal squamous intraepithelial neoplasia (LGESIN): ~80% intermediate, ~20% negative.
**High-grade esophageal squamous intraepithelial neoplasia (HGESIN): ~37% intermediate, ~63% strong.


Image:
Definitions:<ref name=pmid21420715/>
*[http://www.hopkins-gi.org/Upload/200708141549_007658241.jpg Barrett's, Low-grade, High-grade (hopkins-gi.org)].<ref>URL: [http://www.hopkins-gi.org/GDL_Disease.aspx?CurrentUDV=31&GDL_Disease_ID=46159D68-6ED3-4F76-895B-99D8BBBB46EF&GDL_DC_ID=E25BDF77-223D-4B6F-9700-5BE41DBDE28B http://www.hopkins-gi.org/GDL_Disease.aspx?CurrentUDV=31&GDL_Disease_ID=46159D68-6ED3-4F76-895B-99D8BBBB46EF&GDL_DC_ID=E25BDF77-223D-4B6F-9700-5BE41DBDE28B]. Accessed on: 7 August 2011.</ref>
*Negative defined as: < 25% of epithelium +ve ''and'' staining only in lower quarter of epithelium.
*Intermediate defined: >=25% and <=50% of epithelium +ve ''and'' only in the lower half of the epithelium.
*Strong defined: >50% of epithelium +ve ''or'' upper half of epithelium.


==Leiomyoma of the esophagus==
==Leiomyoma of the esophagus==
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*Benign.
*Benign.
*Uncommon.
*Uncommon.
**Before the time of [[GIST]]s - this was a relatively common diagnosis.
*Like [[leiomyoma]]s elswhere.
*Like [[leiomyoma]]s elswhere.


Line 484: Line 443:
DDx:
DDx:
*[[Gastrointestinal stromal tumour]].
*[[Gastrointestinal stromal tumour]].
*[[Schwannoma]].


==Gastrointestinal stromal tumour==
==Gastrointestinal stromal tumour==
Line 498: Line 458:
*[[Smoking]].
*[[Smoking]].


==Squamous cell carcinoma==
==Squamous cell carcinoma of the esophagus==
{{Main|Squamous carcinoma}}
*[[AKA]] ''esophageal squamous cell carcinoma'', abbreviated ''esophageal SCC''.
Like squamous cell carcinoma elsewhere.
{{Main|Squamous cell carcinoma of the esophagus}}
 
Note:
*Just to make things confusing, the ''Staging'' of early SCC differs from that of early adenocarcinoma!


==Esophageal adenocarcinoma==
==Esophageal adenocarcinoma==
===General===
*[[AKA]] ''adenocarcinoma of the esophagus''.
*Often a prognosis poor - as diagnosed in a late stage.
{{Main|Esophageal adenocarcinoma}}
*May be difficult to distinguish from adenocarcinoma of the stomach.
 
====Tx====
*Adenocarcinoma in situ (AIS) - may be treated with endoscopic mucosal resection & follow-up.<ref name=pmid19306943/>
*Surgery - esophagectomy.
 
====Esophagus vs. stomach====
The convention is it's esophageal if both of the following are true:<ref name=Ref_WMSP168>{{Ref WMSP|168}}</ref>
#Epicenter of tumour is in the esophagus.
#Barrett's mucosa is present.
 
===Microscopic===
Features:
*Adenocarcinoma:
**Cell clusters that form glands.
**Nuclear atypia of malignancy:
***Size variation.
***Shape variation.
***Staining variation.
**Mitoses common.
 
Images:
*[http://commons.wikimedia.org/wiki/File:Esophageal_adenocarcinoma_-_very_low_mag.jpg Esophageal adenocarcinoma - very low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Esophageal_adenocarcinoma_-_intermed_mag.jpg Esophageal adenocarcinoma - intermed. mag. (WC)].
====Grading====
Graded like other adenocarcinoma:<ref name=Ref_WMSP168>{{Ref WMSP|168}}</ref>
*>95 % of tumour in glandular arrangement = ''well-differentiated''.
*95-50% of tumour in glandular arrangement= ''moderately-differentiated''.
*<50% of tumour in glandular arrangment = ''poorly-differentiated''.
 
====Staging====
Early esophageal adenocarcinoma has its own staging system:<ref>{{Cite journal  | last1 = Pech | first1 = O. | last2 = May | first2 = A. | last3 = Rabenstein | first3 = T. | last4 = Ell | first4 = C. | title = Endoscopic resection of early oesophageal cancer. | journal = Gut | volume = 56 | issue = 11 | pages = 1625-34 | month = Nov | year = 2007 | doi = 10.1136/gut.2006.112110 | PMID = 17938435 | PMC = 2095648 }}</ref><ref>{{Cite journal  | last1 = Thosani | first1 = N. | last2 = Singh | first2 = H. | last3 = Kapadia | first3 = A. | last4 = Ochi | first4 = N. | last5 = Lee | first5 = JH. | last6 = Ajani | first6 = J. | last7 = Swisher | first7 = SG. | last8 = Hofstetter | first8 = WL. | last9 = Guha | first9 = S. | title = Diagnostic accuracy of EUS in differentiating mucosal versus submucosal invasion of superficial esophageal cancers: a systematic review and meta-analysis. | journal = Gastrointest Endosc | volume =  | issue =  | pages =  | month = Nov | year = 2011 | doi = 10.1016/j.gie.2011.09.016 | PMID = 22115605 | URL = http://www.sciencedirect.com/science/article/pii/S0016510711022048 }}</ref>
*M1 = lamina propria.
*M2 = superficial muscularis mucosae.
*M3 = submucosa.
*M4 = muscularis propria.
 
===IHC===
*CK7 +ve.
*CK20 +ve.
 
To rule-out SCC:
*p63 -ve.
*HWMK -ve.


=Weird stuff=
=Weird stuff=
Line 559: Line 471:
*Granular cell tumour.
*Granular cell tumour.
*Squamous papilloma - koilocytes.
*Squamous papilloma - koilocytes.
*Heterotopic gastric mucosa ("inlet patch") - benign appearing gastric mucosa.
*Heterotopic gastric mucosa ("[[inlet patch]]") - benign appearing gastric mucosa.


==Granular cell tumour==
==Granular cell tumour==
Line 572: Line 484:
*Usu. bland (cytologically non-malignant) nuclei.
*Usu. bland (cytologically non-malignant) nuclei.


Images:
====Images====
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544238/figure/fig04/ GCT of the esophagus (nih.gov)].<ref name=pmid23330004>{{Cite journal  | last1 = Terada | first1 = T. | title = A clinicopathologic study of esophageal 860 benign and malignant lesions in 910 cases of consecutive esophageal biopsies. | journal = Int J Clin Exp Pathol | volume = 6 | issue = 2 | pages = 191-8 | month =  | year = 2013 | doi =  | PMID = 23330004 }}</ref>
*[http://commons.wikimedia.org/wiki/File:Granular_cell_tumor_(3)_skin.jpg GCT - skin (WC)].
*[http://commons.wikimedia.org/wiki/File:Granular_cell_tumor_(3)_skin.jpg GCT - skin (WC)].
*[http://commons.wikimedia.org/wiki/File:Granular_cell_tumor_(4)_S-100.JPG GCT - S100 (WC)].
*[http://commons.wikimedia.org/wiki/File:Granular_cell_tumor_(4)_S-100.JPG GCT - S100 (WC)].
Line 580: Line 493:


===General===
===General===
*Rare & benign condition that resolves without last pathology.<ref name=pmid19809273/>  
*Rare & benign condition that resolves without lasting pathology.<ref name=pmid19809273/>  
**Case report - chronic with strictures.<ref>{{Cite journal  | last1 = Coppola | first1 = D. | last2 = Lu | first2 = L. | last3 = Boyce | first3 = HW. | title = Chronic esophagitis dissecans presenting with esophageal strictures: a case report. | journal = Hum Pathol | volume = 31 | issue = 10 | pages = 1313-7 | month = Oct | year = 2000 | doi = 10.1053/hupa.2000.18470 | PMID = 11070124 }}
**Case report - chronic with strictures.<ref>{{Cite journal  | last1 = Coppola | first1 = D. | last2 = Lu | first2 = L. | last3 = Boyce | first3 = HW. | title = Chronic esophagitis dissecans presenting with esophageal strictures: a case report. | journal = Hum Pathol | volume = 31 | issue = 10 | pages = 1313-7 | month = Oct | year = 2000 | doi = 10.1053/hupa.2000.18470 | PMID = 11070124 }}
</ref>
</ref>
Line 593: Line 506:


==Glycogenic acanthosis of the esophagus==
==Glycogenic acanthosis of the esophagus==
{{Main|Glycogenic acanthosis of the esophagus}}
==Achalasia==
{{main|Achalasia}}
==Esophageal inlet patch==
*[[AKA]] ''inlet patch'', [[AKA]] ''cervical inlet patch''.
===General===
===General===
*Uncommon.
*Benign and likely not of any significance.<ref name=pmid23372354/>
*Benign.
*Possible association with ingestion of hot liquids.<ref name=pmid20524767/>


===Gross/endoscopic===
===Gross===
*Distinctive endoscopic appearance - grey/white raised lesion.<ref name=pmid20524767>{{Cite journal  | last1 = Lopes | first1 = S. | last2 = Figueiredo | first2 = P. | last3 = Amaro | first3 = P. | last4 = Freire | first4 = P. | last5 = Alves | first5 = S. | last6 = Cipriano | first6 = MA. | last7 = Gouveia | first7 = H. | last8 = Sofia | first8 = C. | last9 = Correia-Leitão | first9 = M. | title = Glycogenic acanthosis of the esophagus: an unusually endoscopic appearance. | journal = Rev Esp Enferm Dig | volume = 102 | issue = 5 | pages = 341-2 | month = May | year = 2010 | doi = | PMID = 20524767 | URL = http://www.grupoaran.com/mrmUpdate/lecturaPDFfromXML.asp?IdArt=4618820&TO=RVN&Eng=1 }}</ref>  
*Proximal esophagus - salmon coloured lesion.<ref name=pmid23372354>{{Cite journal  | last1 = Chong | first1 = VH. | title = Clinical significance of heterotopic gastric mucosal patch of the proximal esophagus. | journal = World J Gastroenterol | volume = 19 | issue = 3 | pages = 331-8 | month = Jan | year = 2013 | doi = 10.3748/wjg.v19.i3.331 | PMID = 23372354 }}</ref>


===Microscopic===
===Microscopic===
Features:<ref name=pmid20524767/>
Features:
*Squamous epithelium with:
*Gastric mucosa.<ref name=pmid22091379/>
**Superficial clearing of the cytoplasm.
 
**Thickening.
Image:
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3197178/figure/fig4/ Esophageal inlet patch (nih.gov)].<ref name=pmid22091379>{{Cite journal  | last1 = Behrens | first1 = C. | last2 = Yen | first2 = PP. | title = Esophageal inlet patch. | journal = Radiol Res Pract | volume = 2011 | issue =  | pages = 460890 | month =  | year = 2011 | doi = 10.1155/2011/460890 | PMID = 22091379 }}</ref>


Images:
===Sign out===
*[http://scielo.isciii.es/pdf/diges/v102n5/carta3.pdf Glycogenic acanthosis (isciii.es)].
<pre>
Esophagus at 22 cm, Biopsy:
    - Gastric type mucosa with mild chronic inactive inflammation, see comment.
    - Scant unremarkable squamous epithelium.
    - NEGATIVE for intestinal metaplasia.
    - NEGATIVE for dysplasia.


==Achalasia==
Comment:
===General===
This is in keeping with an "inlet patch", also known as "heterotopic gastric mucosal patch of the proximal esophagus".
*Uncommon.
</pre>
*Risk factor for squamous cell carcinoma (in men and women) and adenocarcinoma (in men).<ref>{{Cite journal  | last1 = Zendehdel | first1 = K. | last2 = Nyrén | first2 = O. | last3 = Edberg | first3 = A. | last4 = Ye | first4 = W. | title = Risk of esophageal adenocarcinoma in achalasia patients, a retrospective cohort study in Sweden. | journal = Am J Gastroenterol | volume = 106 | issue = 1 | pages = 57-61 | month = Jan | year = 2011 | doi = 10.1038/ajg.2010.449 | PMID = 21212754 }}</ref>


===Microscopic===
==Squamous papilloma of the esophagus==
Features:
{{Main|Squamous papilloma of the esophagus}}
*Mucosa usually normal.<ref name=pmid16128783>{{Cite journal  | last1 = Kjellin | first1 = AP. | last2 = Ost | first2 = AE. | last3 = Pope | first3 = CE. | title = Histology of esophageal mucosa from patients with achalasia. | journal = Dis Esophagus | volume = 18 | issue = 4 | pages = 257-61 | month =  | year = 2005 | doi = 10.1111/j.1442-2050.2005.00478.x | PMID = 16128783 }}</ref>


=See also=
=See also=
Line 627: Line 549:


[[Category:Gastrointestinal pathology]]
[[Category:Gastrointestinal pathology]]
[[Category:Esophagus|Esophagus]]
Michael
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