Difference between revisions of "Esophagus"

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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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| -
| -
| -
| -
| 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
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| -
| -
| 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  
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| 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==
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{{Main|Candidiasis}}
{{Main|Candidiasis}}
*[[AKA]] ''esophageal candidiasis''.
*[[AKA]] ''esophageal candidiasis''.
====Sign out====
<pre>
ESOPHAGUS, BIOPSY:
- ESOPHAGITIS WITH FUNGAL ORGANISMS CONSISTENT WITH CANDIDA.
</pre>


====Gross (endoscopic)====
====Gross (endoscopic)====
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====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'''.


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


===Cytomegalovirus esophagitis===
===Cytomegalovirus esophagitis===
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===Herpes esophagitis===
===Herpes esophagitis===
====General====
{{Main|Herpes esophagitis}}
Etiology:
*[[Herpes simplex virus]].
 
====Gross/endoscopic====
Features:
*Ulcers with a "punched-out" appearance with a brown/red edge.
 
Images:
*[http://library.med.utah.edu/WebPath/GIHTML/GI003.html Herpes esophagitis - gross (utah.edu)].
*[http://www.gastrohep.com/images/image.asp?id=648 Herpes esophagitis - endoscopy (gastrohep.com)].
*[http://commons.wikimedia.org/wiki/File:Herpes_esophagitis.JPG Herpes eosphagitis - endoscopy (WC)].
====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:
*Intraepithelial cells with irregular nuclear contours, "squiggle cells" (T lymphocytes<ref name=pmid7587806>{{Cite journal  | last1 = Cucchiara | first1 = S. | last2 = D'Armiento | first2 = F. | last3 = Alfieri | first3 = E. | last4 = Insabato | first4 = L. | last5 = Minella | first5 = R. | last6 = De Magistris | first6 = TM. | last7 = Scoppa | first7 = A. | title = Intraepithelial cells with irregular nuclear contours as a marker of esophagitis in children with gastroesophageal reflux disease. | journal = Dig Dis Sci | volume = 40 | issue = 11 | pages = 2305-11 | month = Nov | year = 1995 | doi =  | PMID = 7587806 }}</ref>), may mimic [[neutrophil]]s.
 
DDx:
*[[Eosinophilic esophagitis]] - characterized by similar histomorphologic features. The key difference is: more [[eosinophil]]s.
 
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==
*Abbreviated ''EE''.
*Abbreviated ''EE''.
===General===
{{Main|Eosinophilic esophagitis}}
*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>
 
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.
 
DDx (endoscopic):
*[[Candida esophagitis]]
 
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>
**Interrater variability is low, i.e. good, if the procedure standardized.<ref name=pmid19830560>{{Cite journal  | last1 = Dellon | first1 = ES. | last2 = Fritchie | first2 = KJ. | last3 = Rubinas | first3 = TC. | last4 = Woosley | first4 = JT. | last5 = Shaheen | first5 = NJ. | title = Inter- and intraobserver reliability and validation of a new method for determination of eosinophil counts in patients with esophageal eosinophilia. | journal = Dig Dis Sci | volume = 55 | issue = 7 | pages = 1940-9 | month = Jul | year = 2010 | doi = 10.1007/s10620-009-1005-z | 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"; ''[[onlinepathology]]'' sees this definition as garbage, as "HPF" is not defined (see [[HPFitis]]).
**There is a consensus paper<ref name=pmid17919504>{{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>
 
DDx:<ref name=Ref_Odze244>{{Ref Odze|244}}</ref>
*[[Gastroesophageal reflux disease]] - no mid and proximal involvement.
*[[Infectious esophagitis]].
*Eosinophilic gastroenteritis.
*Hypereosinophilic syndrome.
 
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/>
 
===Sign out===
<pre>
ESOPHAGUS, DISTAL, BIOPSY:
- SQUAMOUS MUCOSA WITH BASAL CELL HYPERPLASIA, ABUNDANT INTRAEPITHELIAL EOSINOPHILS,
  EDEMA, AND PAPILLARY ELONGATION, SEE COMMENT.
- STAINS (PAS-D, GMS) NEGATIVE FOR MICROORGANISMS.
- NEGATIVE FOR INTESTINAL METAPLASIA.
- NEGATIVE FOR DYSPLASIA.
 
COMMENT:
There are approximately 65 eosinophils per 0.2376 mm*mm (1 HPF).
 
Literature valves show a large variation when defining eosinophilic esophagitis
and frequently use "HPF" as a measure of area, which is not a standardized measure.
[Am. J. Gastroenterol. 102 (10): 2300–13.]
 
Common cut-points are 15 eosinophils/HPF and 20 eosinophils/HPF, where HPF is
often undefined.
 
The above findings are suggestive of eosinophilic esophagitis in the proper
clinical context.
</pre>


==Erosive esophagitis==
==Erosive esophagitis==
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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}}
:''Intestinal metaplasia of the esophagus'' redirects here.
*Abbreviated ''BE''.
===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 (pH 2.5)<ref name=pmid10517897>{{Cite journal  | last1 = Voutilainen | first1 = M. | last2 = Färkkilä | first2 = M. | last3 = Juhola | first3 = M. | last4 = Mecklin | first4 = JP. | last5 = Sipponen | first5 = P. | title = Complete and incomplete intestinal metaplasia at the oesophagogastric junction: prevalences and associations with endoscopic erosive oesophagitis and gastritis. | journal = Gut | volume = 45 | issue = 5 | pages = 644-8 | month = Nov | year = 1999 | doi =  | PMID = 10517897 |URL = http://gut.bmj.com/content/45/5/644.full }}</ref> - goblet cells +ve.
==Barrett esophagus==
 
{{Main|Barrett esophagus}}
===Sign-out===
<pre>
ESOPHAGUS, DISTAL, BIOPSY:
- COLUMNAR EPITHELIUM WITH INTESTINAL METAPLASIA AND MILD ACUTE INFLAMMATION, SEE COMMENT.
- REACTIVE SQUAMOUS EPITHELIUM.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.
 
COMMENT:
The findings are consistent with Barrett's esophagus in the appropriate endoscopic setting.
</pre>
 
<pre>
ESOPHAGUS, DISTAL, BIOPSY:
- COLUMNAR EPITHELIUM WITH INTESTINAL METAPLASIA AND MODERATE CHRONIC INFLAMMATION, SEE COMMENT.
- REACTIVE SQUAMOUS EPITHELIUM.
- NEGATIVE FOR DYSPLASIA AND MALIGNANCY.
 
COMMENT:
The findings are consistent with Barrett's esophagus in the appropriate endoscopic setting.
</pre>
 
<pre>
ESOPHAGUS, DISTAL, BIOPSY:
- COLUMNAR EPITHELIUM WITH EXTENSIVE INTESTINAL METAPLASIA, ACUTE AND CHRONIC INFLAMMATION;
- SEE COMMENT.
- REACTIVE SQUAMOUS EPITHELIUM.
- NEGATIVE FOR DYSPLASIA AND MALIGNANCY.
 
COMMENT:
The columnar epithelium with intestinal metplasia is seen located deep to the squamous
epithelium.
 
The findings are consistent with Barrett's esophagus in the appropriate endoscopic setting.
</pre>


=Neoplastic=
=Neoplastic=
Line 519: Line 390:
*[[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]] ''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>
* [[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===
*Arises in the setting of ''[[Barrett esophagus]]''.
*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/>
====Classification====
*Not very common in North America.
#Indefinite for dysplasia.
#*[[Diagnosis]] used in the context of uncertainty (like ''[[gynecologic cytopathology|ASCUS]]'' and ''[[prostate gland|ASAP]]''); the classic reason for its use is: the surface (epithelium) cannot be seen (which precludes assessment of maturation); may be used in the context of inflammation.
#Low grade dysplasia.
#High grade dysplasia.
 
====Management====
Low grade dysplasia & indefinite for dysplasia:
*Follow-up.
 
High grade dysplasia:
*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>
*Surgical resection (esophagectomy).


===Microscopic===
===Microscopic===
Features to assess:<ref name=Ref_GLP46>{{Ref GLP|46}}</ref>
Features:
# Lack of surface maturation.
*Squamous cell nuclear atypia.
#*Lack of lighter staining at surface.
*Lack of maturation to the 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:
Note:
#No desmoplasia.
*Grading differences between Western pathologists and those of the east.<ref name=pmid11936262/>
#*Stromal fibrotic reaction to the tumour.
#**Desmoplasia is rare in the superficial esophagus.<ref name=Ref_GLP49>{{Ref GLP|49}}</ref>
#No single cells.
#No extensive back-to-back glands.


Notes:  
DDx:
*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.
*Reactive changes.
*Presence of goblet cells suggests it is not dysplasia.<ref>GAG. January 2009.</ref>
*[[Esophageal squamous cell carcinoma]].
*Desmoplasia present = invasive adenocarcinoma.<ref name=Ref_GLP54>{{Ref GLP|54}}</ref>
*Some literature suggests community pathologists should ''not'' make this call, i.e. it should be diagnosed by an expert.<ref name=pmid10385717>{{Cite journal  | last1 = Alikhan | first1 = M. | last2 = Rex | first2 = D. | last3 = Khan | first3 = A. | last4 = Rahmani | first4 = E. | last5 = Cummings | first5 = O. | last6 = Ulbright | first6 = TM. | title = Variable pathologic interpretation of columnar lined esophagus by general pathologists in community practice. | journal = Gastrointest Endosc | volume = 50 | issue = 1 | pages = 23-6 | month = Jul | year = 1999 | doi =  | PMID = 10385717 }}</ref>


Image:
====Images====
*[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>
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>
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544238/figure/fig05/ Mild squamous dysplasia (nih.gov)].
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544238/figure/fig06/ Moderate squamous dysplasia (nih.gov)].
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544238/figure/fig07/ Severe squamous dysplasia (nih.gov)].
*[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)].


===Sign out===
===IHC===
<pre>
*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>
ESOPHAGUS, DISTAL, BIOPSY:
**Reactive changes/normal: ~98% negative, ~2% intermediate.
- LOW-GRADE COLUMNAR EPITHELIAL DYSPLASIA, SEE COMMENT.
**Low-grade esophageal squamous intraepithelial neoplasia (LGESIN): ~80% intermediate, ~20% negative.
- COLUMNAR EPITHELIUM WITH GOBLET CELL METAPLASIA.
**High-grade esophageal squamous intraepithelial neoplasia (HGESIN): ~37% intermediate, ~63% strong.
- REACTIVE SQUAMOUS EPITHELIUM.


COMMENT:
Definitions:<ref name=pmid21420715/>
This was reviewed with Dr. X and they agree with the diagnosis.
*Negative defined as: < 25% of epithelium +ve ''and'' staining only in lower quarter of epithelium.
</pre>
*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==
Line 614: Line 460:
==Squamous cell carcinoma of the esophagus==
==Squamous cell carcinoma of the esophagus==
*[[AKA]] ''esophageal squamous cell carcinoma'', abbreviated ''esophageal SCC''.
*[[AKA]] ''esophageal squamous cell carcinoma'', abbreviated ''esophageal SCC''.
{{Main|Squamous carcinoma}}
{{Main|Squamous cell carcinoma of the esophagus}}
===General===
*Like squamous cell carcinoma elsewhere.
 
Risk factors:<ref name=Ref_APBR104>{{Ref APBR|104 Q1}}</ref>
*Alcohol consumption.
*Tobacco use.
*Food with nitrosamines.
*Burning-hot beverages.
 
Note:
*Reflux is ''not'' a risk factor for esophageal SCC.
 
===Microscopic===
:See ''[[Squamous carcinoma]]''.
 
Note:
*Just to make things confusing, the ''Staging'' of early SCC differs from that of early adenocarcinoma!


==Esophageal adenocarcinoma==
==Esophageal adenocarcinoma==
*[[AKA]] ''adenocarcinoma of the esophagus''.
*[[AKA]] ''adenocarcinoma of the esophagus''.
 
{{Main|Esophageal adenocarcinoma}}
===General===
*Often a prognosis poor - as diagnosed in a late stage.
*May be difficult to distinguish from adenocarcinoma of the stomach.
**By convention (in the ''[[CAP checklist]]'') gastroesophageal junction carcinomas are staged as esophageal carcinomas.<ref>URL: [http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Esophagus_11protocol.pdf http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Esophagus_11protocol.pdf]. Accessed on: 6 April 2012.</ref>
 
====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 690: 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 703: 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 724: 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===
*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>


===Gross/endoscopic===
===Microscopic===
*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>  
Features:
*Gastric mucosa.<ref name=pmid22091379/>


Image:
Image:
*[http://en.wikipedia.org/wiki/File:Glycogenic_acanthosis.jpg Glycogenic acanthosis (WP)].
*[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>
===Microscopic===
Features:<ref name=pmid20524767/>
*Squamous epithelium with:
**Superficial clearing of the cytoplasm.
**Thickening.


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 [[esophageal adenocarcinoma|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 760: Line 549:


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

Latest revision as of 22:57, 27 January 2022

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 esophagus

General:

  • Stratified squamous non-keratinized epithelium.

Normal (esophageal) squamous epithelium:

  • Should "mature" to the surface like good stratified squamous epithelium does.
    • No nuclei at luminal surface.
    • Cells should become less hyperchromatic as you go toward the lumen.
    • Mitoses should be rare and should NOT be above the basal layer.
  • Inflammatory cells should be very rare.

Sign out

Nonspecific inflammation

Esophagus, Distal, Biopsy:
- Columnar epithelium with moderate chronic inflammation.
- Reactive squamous epithelium.
- NEGATIVE for intestinal metaplasia.
- NEGATIVE for dysplasia and NEGATIVE for malignancy.

Block letters

ESOPHAGUS, DISTAL, BIOPSY:
- COLUMNAR EPITHELIUM WITH MODERATE CHRONIC INFLAMMATION.
- REACTIVE SQUAMOUS EPITHELIUM.
- NEGATIVE FOR INTESTINAL METAPLASIA.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.

Diagnoses

Common

  • Normal.
  • Metaplasia (Barrett's esophagus).
  • Dysplasia.
  • Adenocarcinoma.

Less common

  • Squamous cell carcinoma.
  • Eosinophilic esophagitis.
  • Candidiasis.
  • CMV esophagitis.

Tabular summary

Simplified overview

Entity Key feature Other features IHC/Special Clinical Image
Normal squamous epi. matures to surface no inflammation, no atypia - -
Normal esophagus. (WC)
GERD inflammation (eosinophils, lymphocytes) elongated (epithelial) papillae, basal cell hyperplasia incr. risk of Barrett's
c/w GERD. (WC)
Eosinophilic esophagitis abundant eosinophils elongated (epithelial) papillae, basal cell hyperplasia, lymphocytes unresponsive to PPIs
Eosinophilic esophagitis. (WC/Nephron)
Barrett's type change goblet cells no dysplasia Alcian blue +ve incr. risk of adenocarcinoma
Barrett's esophagus. Alcian blue. (WC)
Dysplasia, low grade nuclear crowding at surface hyperchromasia, mild arch. complexity, no necrosis incr. risk of carcinoma
LGH - intermed. mag.
Dysplasia, high grade cribriforming and/or necrosis nuclei often round & large, hyperchromasia marked incr. risk of carcinoma
HGD - high mag.

Columnar dysplasia

Entity Surface maturation Architecture Cytology Other Clinical Image
Normal matures round glands no nuclear atypia - -
Normal esophagus. (WC)
Barrett's esophagus matures round glands, normal gland density +/-scant nuclear atypia goblet cells clinical diagnosis Image
Indefinite for columnar dysplasia minimal maturation or cannot see surface round glands, normal gland density mild nuclear atypia, nuclear pseudostratification, no necrosis - follow-up Image
Low-grade columnar dysplasia minimal-to-scant maturation round glands, +/-rare budding, increased gland density mild-to-moderate nuclear atypia, nuclear pseudostratification, no necrosis - follow-up
LGH - intermed. mag.
High-grade columnar dysplasia no maturation 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 - EMR, surgery
HGD - high mag.
Intramucosal adenocarcinoma 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 moderate-to-marked nuclear atypia - usu. round large nuclei, hyperchromasia, +/-necrosis - EMR, surgery
Adenocarcinoma - high mag.

Columnar dysplasia - another table

Feature Indefinite for columnar dysplasia Low-grade columnar dysplasia High-grade columnar dysplasia Intramucosal carcinoma (IMCa) Utility
Depth of glands superficial only superficial only superficial/deep deep low vs. high
Gland density normal near normal increased back-to-back low vs. high vs. IMCa
Gland morphology round round irregular/rare cribriforming irregular/cribriform/sheeting low vs. high vs. IMCa
Necrosis none none may be present may be present low vs. high & IMCa
Hyperchromasia +/- present present present indef. vs. low
Palisaded/crowded nuclei present present absent/present uncommon low vs. high
Round nuclei + enlargement absent absent present/absent present low vs. high
Desmoplasia absent absent absent +/- (uncommon) high vs. IMCa
Surface involvement present (required) present (required) +/- +/- low vs. high

Decision tree for columnar dysplasia

Odze has made an algorithm - see: Diagnostic algorithm (nih.gov).[1]

Indications

  • Pyrosis = heartburn.[2]

Infectious esophagitis

Main article: Microorganisms

Is a relatively common problem, especially in those that live at the margins (EtOH abusers) and immunosuppressed individuals (HIV/AIDS).

Useful stains

Overview

  • Candida - worms.
  • HPV - koilocytes.
  • CMV - large nuclei.
  • HIV - non-specific.

Candida esophagitis

Main article: Candidiasis
  • AKA esophageal candidiasis.

Gross (endoscopic)

Features:

  • White patches.

DDx (endoscopic):[3]

Microscopic

Features:

  • Worm-like micro-organisms - key feature.
    • Pseudohyphae (single cells).
    • Thickness ~ 1/3-1/2 of squamous cell nucleus.
    • Should be within (squamous) epithelium.
  • Superficial inflammation - esp. neutrophils - important.

Notes:

  • On top of epithelium does not count,[4] i.e. it is likely an artifact.
  • Bacilli and cocci may accompany the candida. They are typically ignored.

DDx:

Image

  • Esophageal candidiasis. (WC)

Sign out

ESOPHAGUS, BIOPSY:
- ESOPHAGITIS WITH FUNGAL ORGANISMS CONSISTENT WITH CANDIDA.

ESOPHAGUS, BIOPSY:
- ACUTE ESOPHAGITIS WITH FUNGAL ORGANISMS CONSISTENT WITH CANDIDA.
- NEGATIVE FOR INTESTINAL METAPLASIA.
- NEGATIVE FOR DYSPLASIA.

Cytomegalovirus esophagitis

Microscopic

Features:

  • Classically at the base of the ulcer; within endothelial cells - key point.

Note:

  • Biopsying the the base of an ulcer usually just yields (non-diagnostic) necrotic debris; so, clinicians are told to biopsy the edge of the lesion. A suspected CMV infection is the exception to this rule!

Herpes esophagitis

Main article: Herpes esophagitis

Human papillomavirus esophagitis

General:

Microscopic

Features:

  • Koilocytes:
    • Perinuclear clearing.
    • Nuclear changes.
      • Size similar (or larger) to those in the basal layer of the epithelium.
      • Nuclear enlargement should be evident on low power, i.e. 25x. [7]
      • Central location - nucleus should be smack in the middle of the cell.

Images:

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

  • Abbreviated GERD or GORD (gastro-oesophageal reflux disease).
  • AKA reflux esophagitis.
Main article: Gastroesophageal reflux disease

Eosinophilic esophagitis

  • Abbreviated EE.
Main article: Eosinophilic esophagitis

Erosive esophagitis

DDx

Work-up

Pill esophagitis

Classic causes:

Esophageal varices

Main article: Esophageal varices

Acute esophagitis

Main article: Acute esophagitis

Benign esophageal stricture

Main article: Esophageal stricture

Esophageal duplication cyst

Main article: Foregut duplication cyst

Zenker's diverticulum

Main article: Zenker's diverticulum
  • AKA cricopharyngeal diverticulum, pharyngoesophageal diverticulum and hypopharyngeal diverticulum.

Radiation esophagitis

Main article: Radiation esophagitis

Preneoplastic

Barrett esophagus

Main article: Barrett esophagus

Neoplastic

Columnar dysplasia of the esophagus

  • AKA esophageal columnar dysplasia, abbreviated ECD.[5]
  • AKA dysplasia in the columnar-lined esophagus.[6]
  • AKA columnar epithelial dysplasia.[7]
Main article: Columnar dysplasia of the esophagus

Squamous dysplasia of the esophagus

  • AKA esophageal squamous dysplasia.

General

Microscopic

Features:

  • Squamous cell nuclear atypia.
  • Lack of maturation to the surface.

Note:

  • Grading differences between Western pathologists and those of the east.[8]

DDx:

Images

A set of cases from Japan:[9]

IHC

  • Ki-67 may be useful:[10]
    • Reactive changes/normal: ~98% negative, ~2% intermediate.
    • Low-grade esophageal squamous intraepithelial neoplasia (LGESIN): ~80% intermediate, ~20% negative.
    • High-grade esophageal squamous intraepithelial neoplasia (HGESIN): ~37% intermediate, ~63% strong.

Definitions:[10]

  • 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

Main article: Leiomyoma

General

  • Benign.
  • Uncommon.
    • Before the time of GISTs - this was a relatively common diagnosis.
  • Like leiomyomas elswhere.

Microscopic

See: Leiomyoma.

DDx:

Gastrointestinal stromal tumour

Main article: Gastrointestinal stromal tumour

Cancer

General

Risks:

Squamous cell carcinoma of the esophagus

  • AKA esophageal squamous cell carcinoma, abbreviated esophageal SCC.
Main article: Squamous cell carcinoma of the esophagus

Esophageal adenocarcinoma

  • AKA adenocarcinoma of the esophagus.
Main article: Esophageal adenocarcinoma

Weird stuff

  • Inflammatory polyp - assoc. trauma/previous intervention.
  • Giant fibrovascular polyp - loose connective tissue covered with squamous epithelium.
  • Granular cell tumour.
  • Squamous papilloma - koilocytes.
  • Heterotopic gastric mucosa ("inlet patch") - benign appearing gastric mucosa.

Granular cell tumour

Main article: Granular cell tumour

Microscopic

Features:

  • Abundant eosinophilic granular cytoplasm key feature.
    • Granules:
      • Size: 1-3 micrometers.
      • Poorly demarcated.
  • Usu. bland (cytologically non-malignant) nuclei.

Images

Esophagitis dissecans superficials

General

  • Rare & benign condition that resolves without lasting pathology.[11]
    • Case report - chronic with strictures.[12]
  • Sloughing of large fragments of the esophageal mucosa - seen on endoscopy.

Microscopic

Features:[11]

  • Flaking of superficial squamous epithelium.
  • Focal bullous separation of the layers.
  • Parakeratosis.
  • Variable acute or chronic inflammation.

Glycogenic acanthosis of the esophagus

Main article: Glycogenic acanthosis of the esophagus

Achalasia

Main article: Achalasia

Esophageal inlet patch

  • AKA inlet patch, AKA cervical inlet patch.

General

  • Benign and likely not of any significance.[13]

Gross

  • Proximal esophagus - salmon coloured lesion.[13]

Microscopic

Features:

Image:

Sign out

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.

Comment:
This is in keeping with an "inlet patch", also known as "heterotopic gastric mucosal patch of the proximal esophagus".

Squamous papilloma of the esophagus

Main article: Squamous papilloma of the esophagus

See also

References

  1. ↑ Odze, RD. (Oct 2006). "Diagnosis and grading of dysplasia in Barrett's oesophagus.". J Clin Pathol 59 (10): 1029-38. doi:10.1136/jcp.2005.035337. PMID 17021130.
  2. ↑ URL: http://dictionary.reference.com/browse/pyrosis. Accessed on: 21 June 2010.
  3. ↑ Odze, Robert D.; Goldblum, John R. (2009). Surgical pathology of the GI tract, liver, biliary tract and pancreas (2nd ed.). Saunders. pp. 244. ISBN 978-1416040590.
  4. ↑ ALS. 4 October 2010.
  5. ↑ Feng, W.; Zhou, Z.; Peters, JH.; Khoury, T.; Zhai, Q.; Wei, Q.; Truong, CD.; Song, SW. et al. (Aug 2011). "Expression of insulin-like growth factor II mRNA-binding protein 3 in human esophageal adenocarcinoma and its precursor lesions.". Arch Pathol Lab Med 135 (8): 1024-31. doi:10.5858/2009-0617-OAR2. PMID 21809994.
  6. ↑ Levine, DS. (Sep 1997). "Management of dysplasia in the columnar-lined esophagus.". Gastroenterol Clin North Am 26 (3): 613-34. PMID 9309409.
  7. ↑ Hamilton, SR.; Smith, RR. (Mar 1987). "The relationship between columnar epithelial dysplasia and invasive adenocarcinoma arising in Barrett's esophagus.". Am J Clin Pathol 87 (3): 301-12. PMID 3825997.
  8. ↑ 8.0 8.1 8.2 Dry, SM.; Lewin, KJ. (Feb 2002). "Esophageal squamous dysplasia.". Semin Diagn Pathol 19 (1): 2-11. PMID 11936262.
  9. ↑ 9.0 9.1 Terada, T. (2013). "A clinicopathologic study of esophageal 860 benign and malignant lesions in 910 cases of consecutive esophageal biopsies.". Int J Clin Exp Pathol 6 (2): 191-8. PMID 23330004.
  10. ↑ 10.0 10.1 Wang, WC.; Wu, TT.; Chandan, VS.; Lohse, CM.; Zhang, L. (Oct 2011). "Ki-67 and ProExC are useful immunohistochemical markers in esophageal squamous intraepithelial neoplasia.". Hum Pathol 42 (10): 1430-7. doi:10.1016/j.humpath.2010.12.009. PMID 21420715.
  11. ↑ 11.0 11.1 11.2 Carmack, SW.; Vemulapalli, R.; Spechler, SJ.; Genta, RM. (Dec 2009). "Esophagitis dissecans superficialis ("sloughing esophagitis"): a clinicopathologic study of 12 cases.". Am J Surg Pathol 33 (12): 1789-94. doi:10.1097/PAS.0b013e3181b7ce21. PMID 19809273.
  12. ↑ Coppola, D.; Lu, L.; Boyce, HW. (Oct 2000). "Chronic esophagitis dissecans presenting with esophageal strictures: a case report.". Hum Pathol 31 (10): 1313-7. doi:10.1053/hupa.2000.18470. PMID 11070124.
  13. ↑ 13.0 13.1 Chong, VH. (Jan 2013). "Clinical significance of heterotopic gastric mucosal patch of the proximal esophagus.". World J Gastroenterol 19 (3): 331-8. doi:10.3748/wjg.v19.i3.331. PMID 23372354.
  14. ↑ 14.0 14.1 Behrens, C.; Yen, PP. (2011). "Esophageal inlet patch.". Radiol Res Pract 2011: 460890. doi:10.1155/2011/460890. PMID 22091379.
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