Difference between revisions of "Esophagus"

From Libre Pathology
Jump to navigation Jump to search
m (fix sp)
 
(245 intermediate revisions by the same user not shown)
Line 1: Line 1:
'''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.
Line 12: Line 13:
*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.
Line 23: Line 43:
*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]]).
Line 34: Line 252:
===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'''.
 
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: [http://en.wikipedia.org/wiki/File:Esophageal_candidiasis_(2)_PAS_stain.jpg Esophageal candidiasis (WC)].
=====Image=====
<gallery>
Image:Esophageal_candidiasis_(2)_PAS_stain.jpg | Esophageal candidiasis. (WC)
</gallery>


===Cytomegalovirus esophagitis===
====Sign out====
*[[AKA]] CMV esophagitis.
<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====
Line 95: Line 334:
*[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]].


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


===Microscopy===
==Esophageal varices==
Features:
{{Main|Esophageal varices}}
*Nuclear changes.
**Nuclear hyperchromatism.
**Nuclear crowding.
**Cigar-shaped (ellipical) nuclei.
*Nuclear changes present at surface (not only in gland crypts).<ref>GAG Jan 2009</ref>
**If changes are present at the base but ''not'' at the luminal surface -- it "matures" and is ''not'' dysplasic.


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


===Management===
==Benign esophageal stricture==
Low grade dysplasia.
{{Main|Esophageal stricture}}
*Follow-up.


High grade dysplasia.
==Esophageal duplication cyst==
*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>
{{Main|Foregut duplication cyst}}
*Surgical resection ???


==Gastroesophageal reflux disease==
==Zenker's diverticulum==
===General===
{{Main|Zenker's diverticulum}}
*Abbreviated ''GERD'' and ''GORD'' (gastro-oesophageal reflux disease).
*[[AKA]] ''cricopharyngeal diverticulum'', ''pharyngoesophageal diverticulum'' and ''hypopharyngeal diverticulum''.


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


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


Notes:
=Neoplastic=
*Eosinophilic esophagitis is characterized by similar histomorphologic features -- key difference: more eosinophils.
==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}}


==Eosinophilic esophagitis==
==Squamous dysplasia of the esophagus==
*[[AKA]] ''esophageal squamous dysplasia''.
===General===
===General===
Clinical:
*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>
*Dyspepsia.
*Common in China.<ref name=pmid11936262/>
**Often mimics gastroesophageal reflux (GERD).<ref name=pmid19596009>PMID 19596009.</ref>
*Not very common in North America.
*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>


Biopsies:
===Microscopic===
*Should be taken from: upper, mid, lower and submitted in separate containers (eosinophilia present through-out-- to differentiate from GERD).
Features:
*Squamous cell nuclear atypia.
*Lack of maturation to the surface.


Associations:
Note:
*Atopy.<ref name=Ref_GLP19>{{Ref GLP|19}}</ref>
*Grading differences between Western pathologists and those of the east.<ref name=pmid11936262/>
*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===
DDx:
*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 }}
*Reactive changes.
</ref>
*[[Esophageal squamous cell carcinoma]].
**[[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)].
====Images====
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)].


===Microscopy===
===IHC===
Features:<ref name=Ref_GLP19>{{Ref GLP|19}}</ref>
*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>
*Mucosa with "abundant eosinophils".
**Reactive changes/normal: ~98% negative, ~2% intermediate.
*Basal cell hyperplasia.
**Low-grade esophageal squamous intraepithelial neoplasia (LGESIN): ~80% intermediate, ~20% negative.
*Papillae elongated.
**High-grade esophageal squamous intraepithelial neoplasia (HGESIN): ~37% intermediate, ~63% strong.


Notes:
Definitions:<ref name=pmid21420715/>
*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>
*Negative defined as: < 25% of epithelium +ve ''and'' staining only in lower quarter of epithelium.
**The group that published the article cited above did another one... <ref name=pmid19830560>PMID 19830560.</ref>
*Intermediate defined: >=25% and <=50% of epithelium +ve ''and'' only in the lower half of the epithelium.
*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).
*Strong defined: >50% of epithelium +ve ''or'' upper half of epithelium.
*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>


===Treatment===
==Leiomyoma of the esophagus==
*Avoid exacerbating antigens.
{{Main|Leiomyoma}}
*Topical corticosteroids, e.g. fluticasone.
===General===
*Benign.
*Uncommon.
**Before the time of [[GIST]]s - this was a relatively common diagnosis.
*Like [[leiomyoma]]s elswhere.


==Erosive esophagitis==
===Microscopic===
===DDx===
:''See: [[Leiomyoma]]''.
*Infections.
*[[Crohn's disease]].
*Pill esophagitis.


===Work-up===
DDx:
*GMS.
*[[Gastrointestinal stromal tumour]].
*PAS.
*[[Schwannoma]].
*[[IHC]] for HSV, CMV.


===Pill esophagitis===
==Gastrointestinal stromal tumour==
Classic causes:
{{Main|Gastrointestinal stromal tumour}}
*Alendronate (Fosamax) - for osteoporosis.
*Iron (can be demonstrated with Prussian blue stain).
*Doxycycline.


==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]].
 
==Squamous cell carcinoma of the esophagus==
*[[AKA]] ''esophageal squamous cell carcinoma'', abbreviated ''esophageal SCC''.
{{Main|Squamous cell carcinoma of the esophagus}}
 
==Esophageal adenocarcinoma==
*[[AKA]] ''adenocarcinoma of the esophagus''.
{{Main|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|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.


==Adenocarcinoma 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===
*Often a prognosis poor - as diagnosed in a late stage.
*Benign and likely not of any significance.<ref name=pmid23372354/>
*May be difficult to distinguish from adenocarcinoma of the stomach.
 
===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===
Features:
*Gastric mucosa.<ref name=pmid22091379/>


===Tx===
Image:
*Adenocarcinoma in situ (AIS) - may be treated with endoscopic mucosal resection & follow-up.<ref name=pmid19306943/>
*[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>
*Surgery - esophagectomy.


===IHC===
===Sign out===
Adenocarcinoma:
<pre>
*CK7 +ve, CK20 +ve.
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".
</pre>


==Weird stuff==
==Squamous papilloma of the esophagus==
*Inflammatory polyp.
{{Main|Squamous papilloma of the esophagus}}
*Giant fibrovascular polyp.
*Granular cell tumour.
*Squamous papilloma.
*Heterotopic gastric mucosa ("inlet patch").


==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]]

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.
Retrieved from "https://librepathology.org/w/index.php?title=Esophagus&oldid=51823"