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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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*Inflammatory cells should be very rare.
*Inflammatory cells should be very rare.


==Diagnoses==
==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=
Common
Common
*Normal.
*Normal.
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*Eosinophilic esophagitis.
*Eosinophilic esophagitis.
*Candidiasis.
*Candidiasis.
*CMV esophagitis.
*[[CMV]] esophagitis.
 
==Tabular summary==
===Simplified overview===
{| class="wikitable"
|'''Entity'''
|'''Key feature'''
|'''Other features'''
|'''IHC/Special'''
|'''Clinical'''
|'''Image'''
|-
|Normal
| squamous epi. matures to surface
| no inflammation, no atypia
| -
| -
| [[Image:Tinci%C3%B3n_hematoxilina-eosina.jpg|center|thumb|125px|Normal esophagus. (WC)]]
|-
|GERD
| inflammation (eosinophils, lymphocytes)
| elongated (epithelial) papillae, basal cell hyperplasia
|
| incr. risk of Barrett's
| [[Image:Gastroesophageal reflux disease -- low mag.jpg|center|thumb|125px|c/w GERD. (WC)]]
|-
|[[Eosinophilic esophagitis]]
| abundant eosinophils
| elongated (epithelial) papillae, basal cell hyperplasia, lymphocytes
|
| unresponsive to PPIs
| [[Image:Eosinophilic_esophagitis_-_2_-_very_high_mag.jpg|center|thumb|125px|Eosinophilic esophagitis. (WC/Nephron)]]
|-
|[[Barrett's esophagus|Barrett's type change]]
| goblet cells
| no dysplasia
| Alcian blue +ve
| incr. risk of adenocarcinoma
| [[Image:Barretts_alcian_blue.jpg|center|thumb|125px|Barrett's esophagus. Alcian blue. (WC)]]
|-
|[[Columnar dysplasia of the esophagus|Dysplasia, low grade]]
| nuclear crowding at surface
| hyperchromasia, mild arch. complexity, no necrosis
|
| incr. risk of carcinoma
| [[Image:Low-grade columnar dysplasia of the esophagus -- intermed mag.jpg|thumb|110px|LGH - intermed. mag.]]
|-
| [[Columnar dysplasia of the esophagus|Dysplasia, high grade]]
| [[cribriform]]ing and/or necrosis
| nuclei often round & large, hyperchromasia
|
| marked incr. risk of carcinoma
| [[Image:High-grade columnar dysplasia of the esophagus -- high mag.jpg|thumb|110px|HGD - high mag.]]
<!--
|Entity
|Key feature
|Other features
|IHC
|Clinical
|Image
|-
-->
|}
 
===Columnar dysplasia===
{| class="wikitable"
|'''Entity'''
|'''Surface maturation'''
|'''Architecture'''
|'''Cytology'''
|'''Other'''
|'''Clinical'''
|'''Image'''
|-
|Normal
| '''matures'''
| round glands
| no nuclear atypia
| -
| -
| [[Image:Tinci%C3%B3n_hematoxilina-eosina.jpg|center|thumb|125px|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
| [[Image:Low-grade columnar dysplasia of the esophagus -- intermed mag.jpg|thumb|110px|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
| [[Image:High-grade columnar dysplasia of the esophagus -- high mag.jpg|thumb|110px|HGD - high mag.]]
|-
|Intramucosal adenocarcinoma
| no maturation
| 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
| -
| [[EMR]], surgery
| [[Image:Esophageal_adenocarcinoma_-_high_mag.jpg|thumb|110px|Adenocarcinoma - high mag.]]
|}
 
===Columnar dysplasia - another table===
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
!'''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: [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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===Useful stains===
===Useful stains===
*PAS.
*PAS.
*Gram stain.
*[[Gram stain]].


===Overview===
===Overview===
*Candida - worms.
*Candida - worms.
*HPV - koilocytes.
*[[HPV]] - koilocytes.
*CMV - large nuclei.
*[[CMV]] - large nuclei.
*[[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'''.


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.


===Cytomegalovirus esophagitis===
DDx:
*[[AKA]] CMV esophagitis.
*[[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>


Clinical:
<pre>
*Classically at the base of the ulcer; within endothelial cells.
ESOPHAGUS, BIOPSY:
- ACUTE ESOPHAGITIS WITH FUNGAL ORGANISMS CONSISTENT WITH CANDIDA.
- NEGATIVE FOR INTESTINAL METAPLASIA.
- NEGATIVE FOR DYSPLASIA.
</pre>


===Herpes esophagitis===
===Cytomegalovirus esophagitis===
====General====
*[[AKA]] [[CMV]] esophagitis.
Etiology:
*Herpes simplex virus.


====Microscopic====
====Microscopic====
Features (3 Ms):
Features:
*'''M'''oulding.
*Classically at the base of the ulcer; within endothelial cells - '''key point'''.
*'''M'''ultinucleation.
 
*'''M'''argination of chromatin.
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!


Images:
===Herpes esophagitis===
*[http://commons.wikimedia.org/wiki/File:Herpes_esophagitis_-_very_high_mag.jpg HSV esophagitis - very high mag. (WC)].
{{Main|Herpes esophagitis}}
*[http://commons.wikimedia.org/wiki/File:Herpes_esophagitis_-_intermed_mag.jpg HSV esophagitis - intermed. mag. (WC)].


===Human papilloma virus esophagitis===
===Human papillomavirus esophagitis===
General:
General:
*[[AKA]] HPV esophagitis.
*[[AKA]] [[HPV]] esophagitis.


====Microscopic====
====Microscopic====
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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)].


==Barrett's esophagus==
=Non-neoplastic disease=
===Definition===
The group of conditions doesn't fit neatly with the others.  It is a mixture of different non-neoplastic conditions.
*Metaplastic transformation of stratified squamous epithelium to simple columnar epithelium with goblet cells.
==Gastroesophageal reflux disease==
*Abbreviated ''GERD'' or ''GORD'' (gastro-oesophageal reflux disease).
*[[AKA]] ''reflux esophagitis''.
{{Main|Gastroesophageal reflux disease}}


===Microscopic===
==Eosinophilic esophagitis==
Features:
*Abbreviated ''EE''.
*Columnar epithelium.
{{Main|Eosinophilic esophagitis}}
*Goblets cells -- '''key feature'''.


===Significance===
==Erosive esophagitis==
*Increased risk of adenocarcinoma of the esophagus.
===DDx===
*Infections.
*[[Crohn's disease]].
*Pill esophagitis.


===Management===
===Work-up===
*Long term follow-up/repeat esophagogastroduodenoscopy.
*[[GMS]].
*[[PAS]].
*[[IHC]] for [[HSV]], [[CMV]].


==Gastroesophageal reflux disease==
===Pill esophagitis===
===General===
Classic causes:
*Abbreviated ''GERD'' and ''GORD'' (gastro-oesophageal reflux disease).
*Alendronate (Fosamax) - for [[osteoporosis]].
*Iron - can be demonstrated with [[Prussian blue stain]].
*Doxycycline.


Clinical:
==Esophageal varices==
*Treated with proton pump inhibitors (PPIs).
{{Main|Esophageal varices}}


===Microscopic===
==Acute esophagitis==
Features:
{{Main|Acute esophagitis}}
#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>
#Papillae elongation.
#Inflammation, esp. eosinophils, lymphocytes with convoluted nuclei ("squiggle cells").
#+/-Spongiosis.


Notes:
==Benign esophageal stricture==
*Eosinophilic esophagitis is characterized by similar histomorphologic features -- key difference: more eosinophils.
{{Main|Esophageal stricture}}


==Eosinophilic esophagitis==
==Esophageal duplication cyst==
===General===
{{Main|Foregut duplication cyst}}
Clinical:
*Dyspepsia.
**Often mimics gastroesophageal reflux (GERD).<ref name=pmid19596009>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:
==Zenker's diverticulum==
*Avoid exacerbating antigens.
{{Main|Zenker's diverticulum}}
*Topical corticosteroids, e.g. fluticasone.
*[[AKA]] ''cricopharyngeal diverticulum'', ''pharyngoesophageal diverticulum'' and ''hypopharyngeal diverticulum''.


Biopsies:
==Radiation esophagitis==
*Should be taken from: upper, mid, lower and submitted in separate containers (eosinophilia present through-out-- to differentiate from GERD).
{{Main|Radiation esophagitis}}


Associations:
=Preneoplastic=
*Atopy.<ref name=Ref_GLP19>{{Ref GLP|19}}</ref>
==Barrett esophagus==
*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>
{{Main|Barrett esophagus}}
*Oral antigens, i.e. particular foods.<ref name=pmid19596009/>
*Familial association.<ref name=pmid19596009/>


===Gross/endoscopic===
=Neoplastic=
*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 }}
==Columnar dysplasia of the esophagus==
</ref>
*[[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]] 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>  
*[[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>
*White.
* [[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}}


Image: [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2841420/figure/F0001/ Trachealization - radiograph (nih.gov)].
==Squamous dysplasia of the esophagus==
*[[AKA]] ''esophageal squamous dysplasia''.
===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.


===Microscopy===
===Microscopic===
Features:<ref name=Ref_GLP19>{{Ref GLP|19}}</ref>
Features:
*Mucosa with "abundant eosinophils".
*Squamous cell nuclear atypia.
*Basal cell hyperplasia.
*Lack of maturation to the surface.
*Papillae elongated.


Notes:
Note:
*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, 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>
*Grading differences between Western pathologists and those of the east.<ref name=pmid11936262/>
**The group that published the article cited above did another one... <ref name=pmid19830560>PMID 19830560.</ref>
*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 rant in the ''[[basics]]'' article).
*The most commonly reported cut points are 15, 20 and 24 eosinophils/HPF, without defining HPF.<ref name=pmid17617209/>
*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>


Image: [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2841420/figure/F0003/ Eosinophilic esophagitis (nih.gov)].
DDx:
*Reactive changes.
*[[Esophageal squamous cell carcinoma]].


==Erosive esophagitis==
====Images====
===DDx===
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>
*Infections.
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544238/figure/fig05/ Mild squamous dysplasia (nih.gov)].
*[[Crohn's disease]].
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544238/figure/fig06/ Moderate squamous dysplasia (nih.gov)].
*Pill esophagitis.
*[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)].


===Work-up===
===IHC===
*GMS.
*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>
*PAS.
**Reactive changes/normal: ~98% negative, ~2% intermediate.
*[[IHC]] for HSV, CMV.
**Low-grade esophageal squamous intraepithelial neoplasia (LGESIN): ~80% intermediate, ~20% negative.
**High-grade esophageal squamous intraepithelial neoplasia (HGESIN): ~37% intermediate, ~63% strong.


===Pill esophagitis===
Definitions:<ref name=pmid21420715/>
Classic causes:
*Negative defined as: < 25% of epithelium +ve ''and'' staining only in lower quarter of epithelium.
*Alendronate (Fosamax) - for osteoporosis.
*Intermediate defined: >=25% and <=50% of epithelium +ve ''and'' only in the lower half of the epithelium.
*Iron (can be demonstrated with Prussian blue stain).
*Strong defined: >50% of epithelium +ve ''or'' upper half of epithelium.
*Doxycycline.


==Dysplasia==
==Leiomyoma of the esophagus==
===Classification===
{{Main|Leiomyoma}}
*Indefinite for dysplasia.
===General===
**Diagnose used in the context of uncertainty (like ''[[gynecologic cytopathology|ASCUS]]'' and ''[[prostate gland|ASAP]]''); usually used in the context of inflammation.
*Benign.
*Low grade dysplasia.
*Uncommon.
*High grade dysplasia.
**Before the time of [[GIST]]s - this was a relatively common diagnosis.
*Like [[leiomyoma]]s elswhere.


===Management===
===Microscopic===
Low grade dysplasia.
:''See: [[Leiomyoma]]''.
*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>
*[[Gastrointestinal stromal tumour]].
*Surgical resection.
*[[Schwannoma]].
 
===Microscopy===
Features:
*Nuclear changes.
**Nuclear hyperchromatism.
**Nuclear crowding.
**Cigar-shaped (ellipical) nuclei.
*Nuclear changes present at surface (not only in gland crypts).<ref>GAG. January 2009.</ref>
**If changes are present at the base but ''not'' at the luminal surface -- it "matures" and is ''not'' dysplasic.


Notes:
==Gastrointestinal stromal tumour==
*Changes similar to those see in colorectal tubular adenomas.
{{Main|Gastrointestinal stromal tumour}}
*Presence of goblet cells is mildly reassuring its not dysplasia.<ref>GAG. January 2009.</ref>


==Cancer==
=[[Cancer]]=
===General===
==General==
*Proximal esophagus: [[squamous cell carcinoma]].
*Proximal esophagus: [[squamous cell carcinoma]].
*Distal esophagus: adenocarcinoma arising from Barrett's esophagus.
*Distal esophagus: adenocarcinoma arising from Barrett's esophagus.


Risks:
Risks:
*EtOH.
*[[Alcohol]] (EtOH).
*Barrett's esophagus.
*Barrett's esophagus.
*Smoking.
*[[Smoking]].


==Adenocarcinoma of the esophagus==
==Squamous cell carcinoma of the esophagus==
===General===
*[[AKA]] ''esophageal squamous cell carcinoma'', abbreviated ''esophageal SCC''.
*Often a prognosis poor - as diagnosed in a late stage.
{{Main|Squamous cell carcinoma of the esophagus}}
*May be difficult to distinguish from adenocarcinoma of the stomach.


===Tx===
==Esophageal adenocarcinoma==
*Adenocarcinoma in situ (AIS) - may be treated with endoscopic mucosal resection & follow-up.<ref name=pmid19306943/>
*[[AKA]] ''adenocarcinoma of the esophagus''.
*Surgery - esophagectomy.
{{Main|Esophageal adenocarcinoma}}


===IHC===
=Weird stuff=
Adenocarcinoma:
*CK7 +ve, CK20 +ve.
 
==Weird stuff==
*Inflammatory polyp - assoc. trauma/previous intervention.
*Inflammatory polyp - assoc. trauma/previous intervention.
*Giant fibrovascular polyp - loose connective tissue covered with squamous epithelium.
*Giant fibrovascular polyp - loose connective tissue covered with squamous epithelium.
*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==
{{Main|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====
*[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_(4)_S-100.JPG GCT - S100 (WC)].
==Esophagitis dissecans superficials==
*[[AKA]] ''sloughing esophagitis''.<ref name=pmid19809273>{{Cite journal  | last1 = Carmack | first1 = SW. | last2 = Vemulapalli | first2 = R. | last3 = Spechler | first3 = SJ. | last4 = Genta | first4 = RM. | title = Esophagitis dissecans superficialis ("sloughing esophagitis"): a clinicopathologic study of 12 cases. | journal = Am J Surg Pathol | volume = 33 | issue = 12 | pages = 1789-94 | month = Dec | year = 2009 | doi = 10.1097/PAS.0b013e3181b7ce21 | PMID = 19809273 }}</ref>
===General===
*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 }}
</ref>
*Sloughing of large fragments of the esophageal mucosa - seen on endoscopy.
===Microscopic===
Features:<ref name=pmid19809273/>
*Flaking of superficial squamous epithelium.
*Focal bullous separation of the layers.
*Parakeratosis.
*Variable acute or chronic inflammation.
==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===
*Rare.
*Benign and likely not of any significance.<ref name=pmid23372354/>
*Usually benign.
 
===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>


===Microscopic===
===Microscopic===
Features:
Features:
*Abundant eosinophilic granular cytoplasm.
*Gastric mucosa.<ref name=pmid22091379/>
 
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>


===Special stains===
===Sign out===
*PAS +ve.
<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.


===IHC===
Comment:
Features:<ref name=pmid20471560>{{Cite journal  | last1 = Rekhi | first1 = B. | last2 = Jambhekar | first2 = NA. | title = Morphologic spectrum, immunohistochemical analysis, and clinical features of a series of granular cell tumors of soft tissues: a study from a tertiary referral cancer center. | journal = Ann Diagn Pathol | volume = 14 | issue = 3 | pages = 162-7 | month = Jun | year = 2010 | doi = 10.1016/j.anndiagpath.2010.01.005 | PMID = 20471560 }}</ref>
This is in keeping with an "inlet patch", also known as "heterotopic gastric mucosal patch of the proximal esophagus".
*S100 +ve.
</pre>
*CD68 +ve (cytoplasmic).
*Vimentin +ve (membranous).


Images:
==Squamous papilloma of the esophagus==
*[http://commons.wikimedia.org/wiki/File:Granular_cell_tumor_(3)_skin.jpg GCT - skin (WC)].
{{Main|Squamous papilloma of the esophagus}}
*[http://commons.wikimedia.org/wiki/File:Granular_cell_tumor_(4)_S-100.JPG GCT - S100 (WC)].


==See also==
=See also=
*[[Stomach]].
*[[Stomach]].
*[[Gastrointestinal pathology]].
*[[Gastrointestinal pathology]].


==References==
=References=
{{reflist|2}}
{{reflist|2}}


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