Difference between revisions of "Uterine cervix"

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Uterine cervix (view source)

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===Surgical specimens===
===Surgical specimens===
# [[Loop electrosurgical excision procedure]] (LEEP).
# [[Loop electrosurgical excision procedure]] (LEEP).
#* [[AKA]] large loop excision of the transformation zone (LLETZ).<ref>{{Cite journal  | last1 = Kenwright | first1 = D. | last2 = Braam | first2 = G. | last3 = Maharaj | first3 = D. | last4 = Langdana | first4 = F. | title = Multiple levels on LLETZ biopsies do not contribute to patient management. | journal = Pathology | volume = 44 | issue = 1 | pages = 7-10 | month = Jan | year = 2012 | doi = 10.1097/PAT.0b013e32834d7b5d | PMID = 22173237 }}</ref><ref>URL: [http://www.webmd.com/cancer/cervical-cancer/loop-electrosurgical-excision-procedure-leep-for-abnormal-cervical-cell-changes http://www.webmd.com/cancer/cervical-cancer/loop-electrosurgical-excision-procedure-leep-for-abnormal-cervical-cell-changes]. Accessed on: 20 March 2014.</ref>
# Radical trachelectomy - removal of the uterine cervix and parametria, preserves fertility.
# Radical trachelectomy - removal of the uterine cervix and parametria, preserves fertility.
# Radical hysterectomy - advanced cervical carcinoma (Stage IA2 and Stage IB1), recurrent carcinoma.<ref name=pmid20871657>{{Cite journal  | last1 = Ware | first1 = RA. | last2 = van Nagell | first2 = JR. | title = Radical hysterectomy with pelvic lymphadenectomy: indications, technique, and complications. | journal = Obstet Gynecol Int | volume = 2010 | issue =  | pages =  | month =  | year = 2010 | doi = 10.1155/2010/587610 | PMID = 20871657 }}</ref>
# Radical hysterectomy - advanced cervical carcinoma (Stage IA2 and Stage IB1), recurrent carcinoma.<ref name=pmid20871657>{{Cite journal  | last1 = Ware | first1 = RA. | last2 = van Nagell | first2 = JR. | title = Radical hysterectomy with pelvic lymphadenectomy: indications, technique, and complications. | journal = Obstet Gynecol Int | volume = 2010 | issue =  | pages =  | month =  | year = 2010 | doi = 10.1155/2010/587610 | PMID = 20871657 }}</ref>
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=Normal histology=
=Normal histology=
Features:
*The uterine cervix consists of non-keratinized squamous epithelium and simple columnar epithelium.   
*The uterine cervix consists of non-keratinized squamous epithelium and simple columnar epithelium.   
*The area of overlap (between squamous & columnar) is known as the "transformation zone".<ref>URL: [http://www.med-ed.virginia.edu/Courses/path/gyn/cervix1.cfm http://www.med-ed.virginia.edu/Courses/path/gyn/cervix1.cfm]. Accessed on: 12 May 2010.</ref>
*The area of overlap (between squamous & columnar) is known as the "transformation zone".<ref>URL: [http://www.med-ed.virginia.edu/Courses/path/gyn/cervix1.cfm http://www.med-ed.virginia.edu/Courses/path/gyn/cervix1.cfm]. Accessed on: 12 May 2010.</ref>
**Also known as "transition zone".  
**Also known as "transition zone".  
Notes:
*Considered from the perspective of histology:
**The squamous component is referred to as the ''exocervix'' (or ''ectocervix''<ref>URL: [http://www.cancer.org/cancer/cervicalcancer/detailedguide/cervical-cancer-what-is-cervical-cancer http://www.cancer.org/cancer/cervicalcancer/detailedguide/cervical-cancer-what-is-cervical-cancer]. Accessed on: 27 January 2014.</ref>).
**The simple columnar (or glandular) component is referred to as the ''endocervix''.
Images:
*[http://www.proteinatlas.org/dictionary/normal/cervix,+uterine+1 Normal cervix (proteinatlas.org)].
==Negative LEEP==
{{Main|LEEP}}


==Transformation zone - biopsy==
==Transformation zone - biopsy==
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Features:
Features:
*Small round cells.
*Small round cells.
*No halos.
*Usually no halos.
**May be seen in pseudokoilocytes.
*No nuclear membrane irregularities.  
*No nuclear membrane irregularities.  
*No nuclear hyperchromasia.


Images:
===Images===
<gallery>
Image: Uterine cervix -- intermed mag.jpg | [[NILM]] with pseudokoilocytes - intermed. mag. (WC)
Image: Uterine cervix -- high mag.jpg | NILM with pseudokoilocytes - high mag. (WC)
Image: Uterine cervix -- very high mag.jpg | NILM with pseudokoilocytes - very high mag. (WC)
Image: Exocervix_--_high_mag.jpg | Benign stripped exocervix - high mag. (WC)
</gallery>
 
www:
*[http://www.flickr.com/photos/euthman/2797778604/in/photostream/ Normal cervix (flickr.com/euthman)].
*[http://www.flickr.com/photos/euthman/2797778604/in/photostream/ Normal cervix (flickr.com/euthman)].
*[http://www.flickr.com/photos/euthman/2796932803/in/photostream/ CIN I versus normal (flickr.com/euthman)].
*[http://www.flickr.com/photos/euthman/2796932803/in/photostream/ CIN I versus normal (flickr.com/euthman)].
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UTERINE ENDOCERVIX, CURETTAGE:  
UTERINE ENDOCERVIX, CURETTAGE:  
- ENDOCERVICAL MUCOSA AND STRIPPED ENDOCERVICAL EPITHELIUM WITHIN NORMAL LIMITS.  
- ENDOCERVICAL MUCOSA AND STRIPPED ENDOCERVICAL EPITHELIUM WITHIN NORMAL LIMITS.  
</pre>
====Inflamed with squamous epithelium====
<pre>
UTERINE ENDOCERVIX, CURETTAGE:
- BENIGN STRIPPED ENDOCERVICAL EPITHELIUM AND SCANT INFLAMED ENDOCERVICAL MUCOSA.
- VERY SCANT SUPERFICIAL SQUAMOUS EPITHELIUM WITHOUT APPARENT PATHOLOGY.
</pre>
</pre>


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- REACTIVE SQUAMOUS EPITHELIUM.
- REACTIVE SQUAMOUS EPITHELIUM.
- NEGATIVE FOR MALIGNANCY.
- NEGATIVE FOR MALIGNANCY.
</pre>
<pre>
UTERINE ENDOCERVIX, CURETTAGE:
- BENIGN INFLAMED ENDOCERVICAL MUCOSA.
- STRIPPED ENDOCERVICAL EPITHELIUM WITHIN NORMAL LIMITS.
</pre>
</pre>


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</pre>
</pre>


Note:
====Limited tissue====
*Some pathologists classify this as ''inadequate''.
<pre>
UTERINE ENDOCERVIX, CURETTAGE:
- ONE MINUTE FRAGMENT OF ENDOCERVICAL EPITHELIUM WITHOUT APPARENT PATHOLOGY,
SEE COMMENT.
- VERY SCANT SUPERFICIAL SQUAMOUS EPITHELIUM WITHOUT APPARENT PATHOLOGY.
 
COMMENT:
The assessment is severely limited by the small amount of tissue. A re-biopsy
should be considered within the clinical context.
</pre>


====Limited tissue====
<pre>
<pre>
UTERINE ENDOCERVIX, CURETTAGE:
UTERINE ENDOCERVIX, CURETTAGE:
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- BENIGN SQUAMOUS EPITHELIUM WITH METAPLASTIC CHANGE.
- BENIGN SQUAMOUS EPITHELIUM WITH METAPLASTIC CHANGE.
- VERY SCANT BENIGN ENDOCERVICAL EPITHELIUM, SUBOPTIMAL SAMPLING.
- VERY SCANT BENIGN ENDOCERVICAL EPITHELIUM, SUBOPTIMAL SAMPLING.
</pre>
<pre>
UTERINE CERVIX, BIOPSY:
- MINUTE FRAGMENTS OF SUPERFICIAL SQUAMOUS EPITHELIUM WITHOUT APPARENT PATHOLOGY.
- SCANT MUCOUS AND INFLAMMATORY CELLS.
- SEE COMMENT.
COMMENT:
The assessment is severely limited by the small amount of tissue. A re-biopsy should be
considered within the clinical context.
</pre>
</pre>


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COMMENT:
COMMENT:
No tissue identified on microscopy. No tissue is seen on inspection of the tissue block.
No tissue identified on microscopy. No tissue is seen on inspection of the paraffin block.
</pre>
</pre>


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#Identify possible endocervical lesions.
#Identify possible endocervical lesions.


=Benign (common)=
==Benign entities of the cervix==
The cervix is ''MANTLED'':
* Mullerian papilloma/Mesonephric hyperplasia/[[Microglandular hyperplasia]].
* [[Arias Stella reaction]].
* [[Nabothian cyst]].
* [[Tunnel cluster]]/Tuboendometrioid metaplasia.
* Lobular endocervical glandular hyperplasia.
* [[Endocervical polyp]]/Endocervicosis/[[Endometriosis]]/Ectopic prostatic tissue.
* Diffuse laminar endocervical hyperplasia.
 
=Benign=
==Nabothian cyst==
==Nabothian cyst==
===General===
===General===
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*[[Benign endocervical polyp]].
*[[Benign endocervical polyp]].


Image:
====Image====
*[http://commons.wikimedia.org/wiki/File:Ovula_nabothi.jpg Nabothian cyst (WC/euthman)].
<gallery>
 
Image:Ovula_nabothi.jpg | Nabothian cyst. (WC/euthman)
</gallery>
===Microscopic===
===Microscopic===
Features:
Features:
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#Important only as one could possibly mistake it as ''[[minimal deviation adenocarcinoma of the uterine cervix|minimal deviation adenocarcinoma]]'', [[AKA]] ''adenoma malignum''.<ref name=pmid2764221>{{cite journal |author=Gilks CB, Young RH, Aguirre P, DeLellis RA, Scully RE |title=Adenoma malignum (minimal deviation adenocarcinoma) of the uterine cervix. A clinicopathological and immunohistochemical analysis of 26 cases |journal=Am. J. Surg. Pathol. |volume=13 |issue=9 |pages=717–29 |year=1989 |month=September |pmid=2764221 |doi= |url=}}</ref>  
#Important only as one could possibly mistake it as ''[[minimal deviation adenocarcinoma of the uterine cervix|minimal deviation adenocarcinoma]]'', [[AKA]] ''adenoma malignum''.<ref name=pmid2764221>{{cite journal |author=Gilks CB, Young RH, Aguirre P, DeLellis RA, Scully RE |title=Adenoma malignum (minimal deviation adenocarcinoma) of the uterine cervix. A clinicopathological and immunohistochemical analysis of 26 cases |journal=Am. J. Surg. Pathol. |volume=13 |issue=9 |pages=717–29 |year=1989 |month=September |pmid=2764221 |doi= |url=}}</ref>  


Images:
====Images====
*[[WC]]:
<gallery>
**[http://commons.wikimedia.org/wiki/File:Tunnel_cluster_-_intermed_mag.jpg Tunnel cluster - intermed. mag. (WC)].
Image:Tunnel_cluster_-_very_low_mag.jpg | Tunnel cluster - very low mag. (WC)
**[http://commons.wikimedia.org/wiki/File:Tunnel_cluster_-_very_high_mag.jpg Tunnel cluster - very high mag. (WC)].
Image:Tunnel_cluster_-_low_mag.jpg | Tunnel cluster - low mag. (WC)
*[[www]]:
Image:Tunnel_cluster_-_intermed_mag.jpg | Tunnel cluster - intermed. mag. (WC)
**[http://surgpath4u.com/caseviewer.php?case_no=477 Tunnel cluster (surgpath4u.com)].
Image:Tunnel_cluster_-_high_mag.jpg | Tunnel cluster - high mag. (WC)
**[http://www.ajronline.org/content/195/2/517/F30.expansion Tunnel cluster (ajronline.org)].
Image:Tunnel_cluster_-_very_high_mag.jpg | Tunnel cluster - very high mag. (WC)
</gallery>
[[www]]:
*[http://surgpath4u.com/caseviewer.php?case_no=477 Tunnel cluster (surgpath4u.com)].
*[http://www.ajronline.org/content/195/2/517/F30.expansion Tunnel cluster (ajronline.org)].


==Microglandular hyperplasia==
==Microglandular hyperplasia==
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*Abbreviated ''MGH''.
*Abbreviated ''MGH''.
*[[AKA]] ''microglandular change''.
*[[AKA]] ''microglandular change''.
===General===
{{Main|Microglandular hyperplasia}}
*Associated with [[OCP]] use.<ref name=pmid10757337>{{Cite journal  | last1 = Zaino | first1 = RJ. | title = Glandular lesions of the uterine cervix. | journal = Mod Pathol | volume = 13 | issue = 3 | pages = 261-74 | month = Mar | year = 2000 | doi = 10.1038/modpathol.3880047 | PMID = 10757337 | URL = http://www.nature.com/modpathol/journal/v13/n3/full/3880047a.html }}</ref>
 
===Microscopic===
Features:<ref name=pmid10757337/>
*Cytologically benign - '''important'''.
**Usually cuboidal morphology.
**Typically clear cytoplasm.
*Crowded small glands (classic), reticular or solid.
 
Significant negatives:
*Nuclear atypia absent.
*[[NC ratio]] not significantly increased.
 
DDx:
*[[Endocervical adenocarcinoma in situ|Adenocarcinoma in situ of the uterine cervix]].
*Endometrial mucinous microglandular adenocarcinoma - very rare.<ref name=pmid16306789>{{Cite journal  | last1 = Giordano | first1 = G. | last2 = D'Adda | first2 = T. | last3 = Gnetti | first3 = L. | last4 = Merisio | first4 = C. | last5 = Melpignano | first5 = M. | title = Endometrial mucinous microglandular adenocarcinoma: morphologic, immunohistochemical features, and emphasis in the human papillomavirus status. | journal = Int J Gynecol Pathol | volume = 25 | issue = 1 | pages = 77-82 | month = Jan | year = 2006 | doi =  | PMID = 16306789 }}</ref><ref name=pmid12808571>{{Cite journal  | last1 = Zamecnik | first1 = M. | last2 = Skalova | first2 = A. | last3 = Opatrny | first3 = V. | title = Microglandular adenocarcinoma of the uterus mimicking microglandular cervical hyperplasia. | journal = Ann Diagn Pathol | volume = 7 | issue = 3 | pages = 180-6 | month = Jun | year = 2003 | doi =  | PMID = 12808571 }}</ref>
*[[Clear cell carcinoma of the uterine cervix]].<ref name=pmid22885379>{{Cite journal  | last1 = Offman | first1 = SL. | last2 = Longacre | first2 = TA. | title = Clear cell carcinoma of the female genital tract (not everything is as clear as it seems). | journal = Adv Anat Pathol | volume = 19 | issue = 5 | pages = 296-312 | month = Sep | year = 2012 | doi = 10.1097/PAP.0b013e31826663b1 | PMID = 22885379 }}</ref>
 
Images:
*[http://www.nature.com/modpathol/journal/v13/n3/fig_tab/3880047f14.html#figure-title MGH (nature.com)].
*[http://sunnybrook.ca/uploads/cx_MGH_5_vd.jpg MGH (sunnybrook.ca)].<ref>URL: [http://sunnybrook.ca/content/?page=Dept_LabS_APath_GynPath_ImgAt_Cvx_neo_micro http://sunnybrook.ca/content/?page=Dept_LabS_APath_GynPath_ImgAt_Cvx_neo_micro]. Accessed on: 25 February 2012.</ref>
 
===IHC===
Features:<ref name=pmid12819393>{{Cite journal  | last1 = Qiu | first1 = W. | last2 = Mittal | first2 = K. | title = Comparison of morphologic and immunohistochemical features of cervical microglandular hyperplasia with low-grade mucinous adenocarcinoma of the endometrium. | journal = Int J Gynecol Pathol | volume = 22 | issue = 3 | pages = 261-5 | month = Jul | year = 2003 | doi = 10.1097/01.PGP.0000071043.12278.8D | PMID = 12819393 }}</ref>
*Ki-67 ~ 0.5% cells.
*Vimentin -ve.
*PR +ve ~ 60% of cases.
*ER +ve/-ve.
 
Others:<ref name=pmid12819393/>
*p53 -ve.
*CEA -ve.
*p16 -ve (scattered cells +ve).{{fact}}
 
===Sign out===
<pre>
UTERINE ENDOCERVIX, CURETTAGE:
- MICROGLANDULAR HYPERPLASIA.
- SQUAMOUS EPITHELIUM WITH REACTIVE CHANGES AND METAPLASTIC CHANGES.
</pre>
 
====Micro====
The sections show gland forming epithelium without nuclear atypia (no nuclear membrane
irregularities, no coarse chromatin). The nuclei are less than 2x the size of a neutrophil,
regularly spaced, pale staining and have small regular nucleoli visible with the 20x
objective. No mitotic activity is apparent.
 
Fragments of reactive squamous epithelium with metaplastic changes are present. Benign
superficial squamous epithelium is identified.


==Wolffian duct hyperplasia==
==Wolffian duct hyperplasia==
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==Squamous metaplasia of the uterine cervix==
==Squamous metaplasia of the uterine cervix==
===General===
*Abbreviated ''SMC''.
*Benign process: columnar cells -> squamoid cells.
{{Main|Squamous metaplasia of the uterine cervix}}
**Biologic response to irritation and/or inflammation.
 
===Gross===
*[[Acetowhite epithelium|Acetowhite lesion]].<ref name=pmid19256708>{{Cite journal  | last1 = Li | first1 = W. | last2 = Venkataraman | first2 = S. | last3 = Gustafsson | first3 = U. | last4 = Oyama | first4 = JC. | last5 = Ferris | first5 = DG. | last6 = Lieberman | first6 = RW. | title = Using acetowhite opacity index for detecting cervical intraepithelial neoplasia. | journal = J Biomed Opt | volume = 14 | issue = 1 | pages = 014020 | month =  | year =  | doi = 10.1117/1.3079810 | PMID = 19256708 }}</ref>
 
===Microscopic===
Features:
* Uniform cell spacing - no crowding - '''key feature'''.
* Nuclei are uniform size and round.
** [[Nucleoli]] present.
*Distinct cell borders
* +/-Intercellular bridges (due to edema) - common.
 
Negatives:
* No mitoses (think cancer/CIN if you see 'em).
* Usually no hyperchromatism (think cancer/CIN if you see it).
 
Notes:
*NC ratio high - possible to confuse with CIN III.
 
DDx:
*[[CIN III]].
*[[Squamous cell carcinoma of the uterine cervix]].
 
Images:
*[http://www.sciencephoto.com/media/294722/view Squamous metaplasia - cervix (sciencephoto.com)].
*[http://commons.wikimedia.org/wiki/File:Bronchial_squamous_metaplasia.jpg Squamous metaplasia - bronchus (WC)].
*[http://nih.techriver.net/patientImages%5C6676.jpg Squamous metaplasia - cytology (techriver.net)].
 
===IHC===
*p16 +ve - in SCC; a poor man's test for [[HPV]].
*Ki-67 - stains a large number of cells; proliferation marker.
 
===Sign out===
====ECC====
<pre>
UTERINE ENDOCERVIX, CURETTAGE:
- SQUAMOUS METAPLASTIC EPITHELIUM.
- VERY SCANT STRIPPED ENDOCERVICAL EPITHELIUM.
</pre>
 
====Cervical biopsy====
<pre>
UTERINE CERVIX, BIOPSY:
- SQUAMOUS METAPLASTIC EPITHELIUM.
- SCANT BENIGN ENDOCERVICAL GLANDS.
</pre>
 
<pre>
UTERINE CERVIX, BIOPSY:
- SQUAMOUS METAPLASTIC EPITHELIUM.
- SCANT BENIGN ENDOCERVICAL GLANDS.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.
</pre>
 
====Micro====
The sections show stratified squamous epithelium. The cells are equally spaced and spaces are seen between the cells (edema). 
 
The nuclei are not significantly enlarged (<3x resting lymphocyte diameter). No nuclear halos are apparent.  The nuclear membranes are regular.  Mild inflammation is present. Nucleoli are present focally.
 
No endocervical cells are identified.


==Reactive squamous epithelium of the uterine cervix==
==Reactive squamous epithelium of the uterine cervix==
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===General===
===General===
*Common.
*Common.
*Individuals with persistent inflammation on [[Pap test]] may have occult [[SIL]].<ref name=pmid21768670>{{Cite journal  | last1 = Bhutia | first1 = K. | last2 = Puri | first2 = M. | last3 = Gami | first3 = N. | last4 = Aggarwal | first4 = K. | last5 = Trivedi | first5 = SS. | title = Persistent inflammation on Pap smear: does it warrant evaluation? | journal = Indian J Cancer | volume = 48 | issue = 2 | pages = 220-2 | month =  | year =  | doi = 10.4103/0019-509X.82901 | PMID = 21768670 }}</ref>


===Microscopic===
===Microscopic===
Line 456: Line 417:
===IHC===
===IHC===
Features:<ref name=pmid8803599>{{Cite journal  | last1 = Marques | first1 = T. | last2 = Andrade | first2 = LA. | last3 = Vassallo | first3 = J. | title = Endocervical tubal metaplasia and adenocarcinoma in situ: role of immunohistochemistry for carcinoembryonic antigen and vimentin in differential diagnosis. | journal = Histopathology | volume = 28 | issue = 6 | pages = 549-50 | month = Jun | year = 1996 | doi =  | PMID = 8803599 }}</ref>
Features:<ref name=pmid8803599>{{Cite journal  | last1 = Marques | first1 = T. | last2 = Andrade | first2 = LA. | last3 = Vassallo | first3 = J. | title = Endocervical tubal metaplasia and adenocarcinoma in situ: role of immunohistochemistry for carcinoembryonic antigen and vimentin in differential diagnosis. | journal = Histopathology | volume = 28 | issue = 6 | pages = 549-50 | month = Jun | year = 1996 | doi =  | PMID = 8803599 }}</ref>
*Vimentin +ve.
*[[Vimentin]] +ve.
*CEA -ve/+ve.
*CEA -ve/+ve.
*p16 -ve.{{fact}}
*p16 -ve.{{fact}}


=Non-invasive=
==Atrophy of the uterine cervix==
==Cervical intraepithelial neoplasia==
*[[AKA]] ''cervical atrophy''.
:''CIN I'', ''CIN II'' and ''CIN III'' redirect to here.
*[[AKA]] ''atrophy of the cervix''.
*Abbreviated ''CIN''.
*[[AKA]] ''cervix with atrophic changes''.
{{Main|Uterine cervix with atrophic changes}}


==Radiation changes of the endocervical epithelium==
{{Main|Radiation changes}}
{{Main|Radiation changes in cervical cytology}}
===General===
===General===
*Refers to changes in squamous epithelium.
*Uncommon.
*Clinical history: radiation treatment for cervical carcinoma.<ref name=pmid2209348/>


Grades (squamous intraepithelial neoplasia):
===Microscopic===
*CIN I = mild dysplasia.
Features:<ref name=pmid2209348>{{Cite journal  | last1 = Frierson | first1 = HF. | last2 = Covell | first2 = JL. | last3 = Andersen | first3 = WA. | title = Radiation changes in endocervical cells in brush specimens. | journal = Diagn Cytopathol | volume = 6 | issue = 4 | pages = 243-7 | month =  | year = 1990 | doi =  | PMID = 2209348 }}</ref>
*CIN II = moderate dysplasia.
*Nuclear enlargement with a normal [[NC ratio]].
*CIN III = severe dysplasia.
*+/-Coarse chromatin.
*+/-Nucleoli.
*+/-Multinucleation - very common.
*Histiocytes - common.


Bethesda system:
==Reactive endocervical cells==
*LSIL ([[low-grade squamous intraepithelial lesion]]) = CIN I.
===General===
*HSIL ([[high-grade squamous intraepithelial lesion]]) = CIN II, CIN III.
*Benign.
 
====Treatment====
*[[LSIL]]: nothing, as usually regress. 
*[[HSIL]]: excision (e.g. cone, [[LEEP]], laser) + follow-up.
 
[[Loop electrosurgical excision procedure]] (LEEP):
*Used for squamous lesions -- pathologist typically gets several pieces.
 
Cone:
*Used for endocervical lesions, i.e. adenocarcinoma in situ (AIS).
*Pathologist gets a ring or donut-shaped piece of tissue.
 
===Gross===
*Acetowhite lesion at colposcopy.


===Microscopic===
===Microscopic===
====Cervical intraepithelial neoplasia I====
Features:
Features - Cervical intraepithelial neoplasia (CIN) I:<ref name=Ref_PBoD1075-6>{{Ref PBoD|1075-6}}</ref>
*Mild nuclear enlargement.
*"Koilocytic atypia":<ref name=Ref_GP146>{{Ref GP|146}}</ref>
*+/-Multinucleation.<ref>URL: [http://www.surgpath4u.com/caseviewer.php?case_no=229 http://www.surgpath4u.com/caseviewer.php?case_no=229]. Accessed on: 2 January 2014.</ref>
**Cytoplasmic halos.
**Nuclear enlargement >=3:1 enlarged nucleus:normal nucleus.
**Nuclear membrane irregularities.
**Nuclear hyperchromasia.
**Coarse chromatin.
**Binucleation may be seen (cytopathic effect of [[HPV]]).<ref name=pmid11491378>{{cite journal |author=Roteli-Martins CM, Derchain SF, Martinez EZ, Siqueira SA, Alves VA, Syrjänen KJ |title=Morphological diagnosis of HPV lesions and cervical intraepithelial neoplasia (CIN) is highly reproducible |journal=Clin Exp Obstet Gynecol |volume=28 |issue=2 |pages=78–80 |year=2001 |pmid=11491378 |doi= |url=}}</ref>
 
Note:
*Atypical cells usually close to basement membrane.
**May be seen, focally, in the upper layers.<ref name=Ref_GP146>{{Ref GP|146}}</ref>
 
Image:
<gallery>
Image:Cervical intraepithelial neoplasia (2) koilocytosis.jpg| CIN I. (WC/KGH)
</gallery>
 
====Cervical intraepithelial neoplasia II====
Features - CIN II:<ref name=Ref_PBoD1075-6>{{Ref PBoD|1075-6}}</ref>
*Increased nuclear-cytoplasmic ratio, loss of polarity, incr. mitoses, hyperchromasia.
**If there are large nuclei... you should seen 'em on low power, i.e. 25x.
 
Image:
<gallery>
Image:Cervical intraepithelial neoplasia (3) CIN2.jpg| CIN I. (WC/KGH)
</gallery>
 
====Cervical intraepithelial neoplasia III====
Features - CIN III:<ref name=Ref_PBoD1075-6>{{Ref PBoD|1075-6}}</ref>
*Same changes as in CIN II + outer third (or full thickness).


Notes:
Notes:
#Hyperchromasia is a very useful feature for identifying CIN (particularly at low power, i.e. 25x).
DDx of multinucleated endocervical cells:
#Koilocytes are the key feature of CIN I.
*[[HSV]].<ref name=pmid4352382>{{Cite journal  | last1 = Naib | first1 = ZM. | last2 = Nahmias | first2 = AJ. | last3 = Josey | first3 = WE. | last4 = Zaki | first4 = SA. | title = Relation of cytohistopathology of genital herpesvirus infection to cervical anaplasia. | journal = Cancer Res | volume = 33 | issue = 6 | pages = 1452-63 | month = Jun | year = 1973 | doi =  | PMID = 4352382 | URL = http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=4352382 }}</ref>
#Koilocytes are ''not'' considered to be part of a CIN II lesion or CIN III lesion.
*Benign endocervical cells.
#Large irregular nuclei are not required for CIN II... but you should think about it.
#Some mild changes at the squamo-columnar junction are expected.
#Look for the location of mitoses...
#* If there is a mitosis in the inner third (of the epithelial layer) = think CIN I. 
#* If there is a mitosis in the middle third (of the epithelial layer) = think CIN II.
#* If there is a mitosis in the outer third = think CIN III.
#Prominent [[nucleoli]] are ''not'' present in CIN.<ref name=Ref_GP146>{{Ref GP|146}}</ref>
#*Nucleoli are common in reactive changes.<ref>STC. January 2009.</ref>
#The most probably place for CIN is the posterior cervix (6 o'clock position) - risk is marginally increased.<ref name=pmid16378031>{{Cite journal  | last1 = Pretorius | first1 = RG. | last2 = Zhang | first2 = X. | last3 = Belinson | first3 = JL. | last4 = Zhang | first4 = WH. | last5 = Ren | first5 = SD. | last6 = Bao | first6 = YP. | last7 = Qiao | first7 = YL. | title = Distribution of cervical intraepithelial neoplasia 2, 3 and cancer on the uterine cervix. | journal = J Low Genit Tract Dis | volume = 10 | issue = 1 | pages = 45-50 | month = Jan | year = 2006 | doi =  | PMID = 16378031 }}
</ref>
 
DDx:
*[[CIN II]].
*[[Squamous cell carcinoma of the uterine cervix]].


=====Images=====
====Images====
<gallery>
<gallery>
Image:Cervical_intraepithelial_neoplasia_(4)_CIN3.jpg| CIN I. (WC/KGH)
Image: Endocervical epithelium with multinucleation -- high mag.jpg | Multinucleated endocervix - high mag.
Image: Endocervical epithelium with multinucleation -- very high mag.jpg | Multinucleated endocervix - very high mag.
Image: Endocervical epithelium with multinucleation -- extremely high mag.jpg | Multinucleated endocervix - extremely high mag.
</gallery>
</gallery>
www:
www:
*[http://www.flickr.com/photos/euthman/6076642630/in/pool-labmed CIN III (flickr.com/euthman)].
*[http://www.surgpath4u.com/caseviewer.php?case_no=229 Reactive endocervical cells (surgpath4u.com)].
*[http://www.flickr.com/photos/euthman/3995927827/in/pool-labmed CIN III (flickr.com/euthman)].
*[http://www.flickriver.com/photos/euthman/tags/hsil/ CIN III - several images (flickriver.com)].


====Koilocytes versus benign squamous====
=Non-invasive=
Koilocytes:
==Cervical intraepithelial neoplasia==
*Perinuclear clearing.
*Previously known as ''cervical intraepithelial neoplasia'' and ''cervical dysplasia''.
*Nuclear changes.
{{Main|Squamous intraepithelial lesion of the uterine cervix}}
**Size similar (or larger) to those in the basal layer of the epithelium.
**Nuclear enlargement should be evident on low power, i.e. 25x. <ref>V. Dube 2008.</ref>
**Central location - nucleus should be smack in the middle of the cell.
 
Notes:
# Both perinuclear clearing and nuclear changes are essential.
# Benign cells have a small nucleus that is peripheral.
 
===IHC===
Features:<ref name=pmid22162342>{{Cite journal  | last1 = Singh | first1 = M. | last2 = Mockler | first2 = D. | last3 = Akalin | first3 = A. | last4 = Burke | first4 = S. | last5 = Shroyer | first5 = A. | last6 = Shroyer | first6 = KR. | title = Immunocytochemical colocalization of P16(INK4a) and Ki-67 predicts CIN2/3 and AIS/adenocarcinoma. | journal = Cancer Cytopathol | volume = 120 | issue = 1 | pages = 26-34 | month = Feb | year = 2012 | doi = 10.1002/cncy.20188 | PMID = 22162342 }}</ref>
*p16.
**Diffuse strong staining involving at least all of the basal aspect of the epithelium = CIN II or CIN III.
**Patchy, weak positive staining = CIN I or squamous metaplasia.
*Ki-67.
**Several positive cells above basal layer suggests CIN II or CIN III.
 
Notes:
*Both p16 and Ki-67 are usually negative in CIN I -- 75% of cases.<ref name=pmid22104735>{{Cite journal  | last1 = Jackson | first1 = JA. | last2 = Kapur | first2 = U. | last3 = Erşahin | first3 = Ç. | title = Utility of p16, Ki-67, and HPV test in diagnosis of cervical intraepithelial neoplasia and atrophy in women older than 50 years with 3- to 7-year follow-up. | journal = Int J Surg Pathol | volume = 20 | issue = 2 | pages = 146-53 | month = Apr | year = 2012 | doi = 10.1177/1066896911427703 | PMID = 22104735 }}</ref>
**CIN I with p16 staining appears to have a higher risk of progression the p16 negative CIN I.<ref name=pmid19683687>{{Cite journal  | last1 = del Pino | first1 = M. | last2 = Garcia | first2 = S. | last3 = Fusté | first3 = V. | last4 = Alonso | first4 = I. | last5 = Fusté | first5 = P. | last6 = Torné | first6 = A. | last7 = Ordi | first7 = J. | title = Value of p16(INK4a) as a marker of progression/regression in cervical intraepithelial neoplasia grade 1. | journal = Am J Obstet Gynecol | volume = 201 | issue = 5 | pages = 488.e1-7 | month = Nov | year = 2009 | doi = 10.1016/j.ajog.2009.05.046 | PMID = 19683687 }}</ref>
 
===Sign-out===
====LEEP====
<pre>
UTERINE CERVIX, LOOP ELECTROSURGICAL EXCISION PROCEDURE (LEEP):
- CERVICAL INTRAEPITHELIAL NEOPLASIA 2 (MODERATE DYSPLASIA).
- DEEP, ENDOCERVICAL AND EXOCERVICAL MARGINS NEGATIVE FOR INTRAEPITHELIAL NEOPLASIA.
</pre>
 
<pre>
UTERINE CERVIX, LOOP ELECTROSURGICAL EXCISION PROCEDURE (LEEP):
- CERVICAL INTRAEPITHELIAL NEOPLASIA 3 (SEVERE DYSPLASIA).
- DEEP, ENDOCERVICAL AND EXOCERVICAL MARGINS NEGATIVE FOR INTRAEPITHELIAL NEOPLASIA.
</pre>
 
<pre>
UTERINE CERVIX, LOOP ELECTROSURGICAL EXCISION PROCEDURE (LEEP):
- CERVICAL INTRAEPITHELIAL NEOPLASIA 3 (SEVERE DYSPLASIA).
- DEEP, ENDOCERVICAL AND EXOCERVICAL MARGINS NEGATIVE FOR INTRAEPITHELIAL NEOPLASIA.
- NEGATIVE FOR MALIGNANCY.
 
COMMENT:
CIN 3 is seen in 2 of 5 blocks and has a total linear extent of 17 millimeters.
</pre>
 
 
====Biopsy====
=====LSIL=====
<pre>
UTERINE CERVIX, BIOPSY:
- LOW-GRADE SQUAMOUS INTRAEPITHELIAL LESION (LSIL).
- NO ENDOCERVICAL EPITHELIUM IDENTIFIED.
</pre>
 
<pre>
UTERINE CERVIX, BIOPSY:
- LOW-GRADE SQUAMOUS INTRAEPITHELIAL LESION (LSIL).
- TRANSFORMATION ZONE PRESENT.
</pre>
 
=====CIN 1=====
<pre>
UTERINE CERVIX, BIOPSY:
- CERVICAL INTRAEPITHELIAL NEOPLASIA 1 (MILD DYSPLASIA).
- TRANSFORMATION ZONE PRESENT.
</pre>
 
<pre>
COMMENT:
The Ki-67 positive cells are confined to the lower aspect of the squamous epithelium. 
A p16 stain is negative.
</pre>
 
=====At least CIN 2=====
<pre>
UTERINE CERVIX, BIOPSY:
- AT LEAST CERVICAL INTRAEPITHELIAL NEOPLASIA 2 (MODERATE DYSPLASIA).
- TRANSFORMATION ZONE PRESENT.
</pre>
 
<pre>
UTERINE ENDOCERVIX, CURETTAGE:
- HIGH-GRADE SQUAMOUS INTRAEPITHELIAL LESION (HSIL).
- ENDOCERVICAL MUCOSA AND STRIPPED ENDOCERVICAL EPITHELIUM WITHIN NORMAL LIMITS.
 
COMMENT:
The HSIL is in keeping with CIN 2.
</pre>
 
=====CIN 3=====
<pre>
UTERINE CERVIX, BIOPSY:
- CERVICAL INTRAEPITHELIAL NEOPLASIA 3 (SEVERE DYSPLASIA).
</pre>
 
<pre>
COMMENT:
A p16 stains marks the full thickness of the epithelium and is strong.  A Ki-67 stain
marks increased numbers of superficial epithelial cells.
</pre>
 
====Micro====
The sections show the transformation zone.
 
The squamous epithelium has an increased nuclear-cytoplasmic ratio, loss of polarity, mitoses and nuclear hyperchromasia extending to the superficial third of the epithelium.  Mitoses are seen in the upper third of the epithelium.  No nucleoli are present. No invasion is identified.
 
The columnar epithelium has focal involvement by the squamous lesion.  There is no columnar dysplasia.  The margins are negative for dysplasia.
 
=====Biopsy=====
The sections show the transformation zone.
 
The squamous epithelium has an increased nuclear-cytoplasmic ratio, loss of polarity,
mitoses and nuclear hyperchromasia extending to the superficial third of the epithelium.
Mitoses are seen in the upper third of the epithelium. Nucleoli are not apparent.
No invasion is identified.
 
No columnar dysplasia is identified.
======Alternate======
The sections show fragments of transformation zone.
 
There is dysplastic squamous epithelium with coarse chromatin, nuclear hyperchromasia,
nuclear enlargement, irregular nuclear membranes, and an increase nuclear-to-cytoplasmic
ratio.  Mitotic activity is abundant focally (5 mitoses/0.2376 mm*mm).  The dysplastic
squamous epithelium does not show appreciable maturation toward the surface (CIN 3).
The dysplastic squamous epithelium is not associated with stroma; thus, the
presence/absence of invasion cannot be assessed.  Small nucleoli are seen rarely.
 
There is benign squamous epithelium. Scant benign stripped endocervical epithelium is
present.


==Endocervical adenocarcinoma in situ==
==Endocervical adenocarcinoma in situ==
:''For the cytology see [[Gynecologic cytopathology#Endocervical adenocarcinoma in situ]]''
:''For the cytology see [[Gynecologic cytopathology#Endocervical adenocarcinoma in situ]]''
*[[AKA]] ''adenocarcinoma in situ'', abbreviated ''AIS''.
*[[AKA]] ''adenocarcinoma in situ'', abbreviated ''AIS''.
===General===
{{Main|Endocervical adenocarcinoma in situ}}
*Usually due to [[HPV]].
*May be found together with squamous neoplasias of the cervix.
*AIS of the cervix is much less common than squamous dysplasia of the cervix/SCC of the cervix.
*Generally, definitely diagnosed with an ''endocervical curettage'' (ECC).
 
===Gross===
*Not apparent at colposcopy.
 
===Microscopic===
Features:<ref name=pmid10757337>{{Cite journal  | last1 = Zaino | first1 = RJ. | title = Glandular lesions of the uterine cervix. | journal = Mod Pathol | volume = 13 | issue = 3 | pages = 261-74 | month = Mar | year = 2000 | doi = 10.1038/modpathol.3880047 | PMID = 10757337 | url = http://www.nature.com/modpathol/journal/v13/n3/full/3880047a.html }}</ref>
#Nuclear changes - '''key feature''':
#*Variable nuclear stratification.
#**Nuclear crowding/pseudostratification.
#*Nuclear enlargement.
#**Often cigar-shaped nuclei.
#*Coarse chromatin.
#*Small nucleolus or [[nucleoli]].
#+/-Mitoses.
#+/-Reduced cytoplasmic mucin.
#Preservation of glandular architecture.
#*Normal gland spacing - lack of complexity ("lobular pattern").
#*Normal gland depth (subjective).
 
DDx:
*[[Tubal metaplasia of the uterine cervix|Tubal metaplasia]].
*[[Arias-Stella reaction]].
*[[Endometriosis]].
*Lower uterine segment epithelium<ref name=Ref_GP167>{{Ref GP|167}}</ref> - esp. [[proliferative phase endometrium]] - mitoses rare, NC ratio normal, stroma different.
*[[Endocervical adenocarcinoma]] - often has paradoxical maturation... paler cytoplasm & nuclei than adjacent AIS.
*[[metastasis|Metastatic]] adenocarcinoma.
 
Images:
*[http://nih.techriver.net/view.php?patientId=99 Endocervical adenocarcinoma in situ (techriver.net)].
*[http://womenshealthsection.com/content/gynpc/gynpc006d.jpg Endocervical adenocarcinoma in situ (womenshealthsection.com)].<ref>URL: [http://www.womenshealthsection.com/content/print.php3?title=gynpc006&cat=60&lng=english http://www.womenshealthsection.com/content/print.php3?title=gynpc006&cat=60&lng=english]. Accessed on: 20 March 2013.</ref>
*[http://nih.techriver.net/view.php?patientId=67 Endocervical adenocarcinoma in situ - cytology (techriver.net)].
 
===IHC===
*p16 +ve.
*CEA +ve.
*Vimentin -ve.


=Cancer=
=Cancer=
Line 735: Line 479:
{{Main|Squamous cell carcinoma}}
{{Main|Squamous cell carcinoma}}
*[[AKA]] ''cervical squamous cell carcinoma''.
*[[AKA]] ''cervical squamous cell carcinoma''.
===General===
{{Main|Squamous cell carcinoma of the uterine cervix}}
*Most common type of cervical cancer.
 
Risk factors:
*Low socioeconomic status.
*Smoking.
*Early first intercourse.
*High risk partners.
*[[Human papillomavirus]] (HPV) infection, esp. "high risk HPV".
**HPV 16 closely assoc. with SCC.<ref name=pmid15551313>{{Cite journal  | last1 = De Boer | first1 = MA. | last2 = Peters | first2 = LA. | last3 = Aziz | first3 = MF. | last4 = Siregar | first4 = B. | last5 = Cornain | first5 = S. | last6 = Vrede | first6 = MA. | last7 = Jordanova | first7 = ES. | last8 = Fleuren | first8 = GJ. | title = Human papillomavirus type 18 variants: histopathology and E6/E7 polymorphisms in three countries. | journal = Int J Cancer | volume = 114 | issue = 3 | pages = 422-5 | month = Apr | year = 2005 | doi = 10.1002/ijc.20727 | PMID = 15551313 }}</ref>
 
===Microscopic===
Features:
*Squamous differentiation.
**+/-Intracellular bridges.
**Scant-to-moderate cytoplasm.
*Penetration of basement membrane.
**May be challenging to determine.
*Nuclear atypia.
 
SCC of the cervix versus CIN III:
Invasive cancer look for:
*Eosinophilia.
*Extra large nuclei, i.e. nuclei 5x normal size.
*Stromal inflammation (lymphocytes, plasma cells).
*Long rete ridges.
*Numerous beeds/blobs of epithelial cells that seem unlikely to be rete ridges.
*[[Desmoplastic stroma]] - increased cellularity, spindle cell morphology.
 
DDx:
* [[Squamous metaplasia of the uterine cervix]] - if you can trace the squamous cells from a gland to the surface it is less likely to be invasive cancer.<ref>[http://www.nature.com/modpathol/journal/v15/n3/pdf/3880520a.pdf http://www.nature.com/modpathol/journal/v15/n3/pdf/3880520a.pdf]</ref>
*[[CIN III]] +/- endocervical gland involvement.
 
Images:
*[http://sunnybrook.ca/uploads/cx_microinv_scc_S10-5249_6.jpg Microinvasive cervical SCC - low mag. (sunnybrook.ca)].<ref name=sb_cx_scc/>
*[http://sunnybrook.ca/uploads/cx_microinv_scc_S10-5249_7.jpg Microinvasive cervical SCC - high mag. (sunnybrook.ca)].<ref name=sb_cx_scc>URL: [http://sunnybrook.ca/content/?page=dept-labs-apath-gynpath-imgat-cvx-mal-microiscc http://sunnybrook.ca/content/?page=dept-labs-apath-gynpath-imgat-cvx-mal-microiscc]. Accessed on: 2 May 2013.</ref>
*[http://missinglink.ucsf.edu/lm/IDS_107_Cervix_Ovary_Uterus/ASSETS/Slide329SCClp_small.JPG Cervical SCC - low mag. (ucsf.edu)].<ref name=uscf>URL: [http://missinglink.ucsf.edu/lm/IDS_107_Cervix_Ovary_Uterus/homepage.htm http://missinglink.ucsf.edu/lm/IDS_107_Cervix_Ovary_Uterus/homepage.htm]. Accessed on: 2 May 2013.</ref>
*[http://missinglink.ucsf.edu/lm/IDS_107_Cervix_Ovary_Uterus/ASSETS/Slide329SCChp.JPG Cervical SCC - high mag. (uscf.edu)].
 
====Grading====
Divided into:<ref>{{Ref PBoD|1077}}</ref>
#Well-differentiated (keratinizing).
#Moderately differentiated (nonkeratinizing).
#Poorly differentiated.
 
====Depth measurement====
*Basement membrane (where it invades) to deepest point.
 
Note:
*Stage Ib - clinical diagnosis.
**Definition of stage Ib: clinically visible.
=====FIGO=====
Microinvasive SCC as per FIGO:
*Depth < 5 mm.
*Width < 7 mm.
*+/-Vascular invasion.
 
=====SGO=====
Microinvasive SCC as per The Society of Gynecologic Oncologists (SGO):
*<= 3 mm.
*Negative for [[vascular invasion]].
 
Note:
*The SGO criteria the prefered by North American gynecologists.
 
===IHC===
*Factor VIII - to look for LVI.
 
===Sign out===
Early invasive SCC - things to report:
*Depth of invasion.
*Length of tumour.
*Number of blocks with tumour.
*LVI.
*Margins.
 
<pre>
UTERINE CERVIX, BIOPSY:
- FRAGMENTS OF INVASIVE SQUAMOUS CELL CARCINOMA.
-- DEPTH OF INVASION AND LENTH OF TUMOUR CANNOT BE ASSESSED.
-- LYMPHOVASCULAR INVASION NOT APPARENT.
</pre>


==Adenocarcinoma of the uterine cervix==
==Adenocarcinoma of the uterine cervix==
*[[AKA]] ''endocervical adenocarcinoma''.
*[[AKA]] ''endocervical adenocarcinoma''.
*[[AKA]] ''cervical adenocarcinoma''.
*[[AKA]] ''cervical adenocarcinoma''.
===General===
{{Main|Adenocarcinoma of the uterine cervix}}
*Adenocarcinoma of the cervix is much less common than squamous dysplasia of the cervix/SCC of the cervix.
*Arises from the endocervical glands.
 
===Microscopic===
Features:
*Stromal changes - "[[desmoplastic stroma]]/[[desmoplastic reaction]]".
**Fibrosis/streaming cells.
*Gland fusion.
*Glands too deep -- very fuzzy criterion.
 
Notes:
*AIS changes - similar to [[colon|colonic]] dysplasia.
*AIS may occur together with CIN.
**Not infrequently they (AIS, CIN) occur together - both are due, indirectly, to HPV infection.
*May be difficult to be certain of invasion.
**A feature suggestive of invasion is ''cytoplasmic eosinophilia''.
 
DDx:
*[[Microglandular hyperplasia]] - [[NC ratio]] normal, no nuclear atypia.
*[[Endocervical adenocarcinoma in situ]].
*Metastatic adenocarcinoma.
 
Images:
*[http://commons.wikimedia.org/wiki/File:Cervical_adenocarcinoma_-_low_mag.jpg Cervical adenocarcinoma - low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Cervical_adenocarcinoma_-_intermed_mag.jpg Cervical adenocarcinoma - intermed. mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Cervical_adenocarcinoma_-_high_mag.jpg Cervical adenocarcinoma - high mag. (WC)].
 
===IHC===
Features for diagnosis:
*p16 +ve.
*Ki-67 -- high.
 
Uterus vs. cervix:<ref>LAE. 15 January 2009.</ref>
*Cervix (typically): CEA +ve, p16 +ve.
**ER -ve, PR -ve, vimentin -ve.
*Uterus (typically): vimentin +ve, ER +ve, PR +ve.
**CEA -ve, p16 -ve.


=Uncommon non-invasive=
=Uncommon non-invasive=
==Stratified mucin-producing intraepithelial lesions of the cervix==
==Stratified mucin-producing intraepithelial lesions of the cervix==
*Abbreviated ''SMILE'' ('''S'''tratified '''M'''ucin-producing '''I'''ntraepithelial '''LE'''sion).
*Abbreviated ''SMILE'' ('''S'''tratified '''M'''ucin-producing '''I'''ntraepithelial '''LE'''sion).
===General===
{{Main|Stratified mucin-producing intraepithelial lesion of the cervix}}
*Rare.
*Often accompanied by [[cervical intraepithelial neoplasia]] and [[adenocarcinoma in situ]].<ref name=pmid11023104/>
 
===Microscopic===
Features:<ref name=pmid11023104>{{Cite journal  | last1 = Park | first1 = JJ. | last2 = Sun | first2 = D. | last3 = Quade | first3 = BJ. | last4 = Flynn | first4 = C. | last5 = Sheets | first5 = EE. | last6 = Yang | first6 = A. | last7 = McKeon | first7 = F. | last8 = Crum | first8 = CP. | title = Stratified mucin-producing intraepithelial lesions of the cervix: adenosquamous or columnar cell neoplasia? | journal = Am J Surg Pathol | volume = 24 | issue = 10 | pages = 1414-9 | month = Oct | year = 2000 | doi =  | PMID = 11023104 }}</ref>
*Stratified epithelium with:
**Nuclear atypia.
**Cytoplasmic clearing or vacuoles in lesions - through-out.
 
DDx:
*[[HSIL]].
**Mucin may be present superficially.<ref name=pmid11023104/>
 
Images:
*[http://sunnybrook.ca/uploads/cx_SMILE_S10-1021_vd_1.jpg SMILE (sunnybrook.ca)].<ref>URL: [http://sunnybrook.ca/content/?page=Dept_LabS_APath_GynPath_ImgAt_Cvx_mal_ais_smile http://sunnybrook.ca/content/?page=Dept_LabS_APath_GynPath_ImgAt_Cvx_mal_ais_smile]. Accessed on: 30 March 2012.</ref>
*[http://sunnybrook.ca/uploads/cx_SMILE_S10-1021_vd_2.jpg SMILE (sunnybrook.ca)].
 
===IHC===
Features:
*Ki-67 high.
*Keratin 14 -ve.
*p63 +ve/-ve -- only basal if positive.


=Uncommon types of cervical cancer=
=Uncommon types of cervical cancer=
Line 899: Line 503:
*Like other [[serous carcinoma]]s.
*Like other [[serous carcinoma]]s.


==Adenosquamous carcinoma==
==Adenosquamous carcinoma of the uterine cervix==
===General===
{{Main|Adenosquamous carcinoma of the uterine cervix}}
*Uncomon.
 
Note:
*[[Glassy cell carcinoma]] is considered to be a subtype of adenosquamous carcinoma.<ref>{{Cite journal  | last1 = Kosińiska-Kaczyńska | first1 = K. | last2 = Mazanowska | first2 = N. | last3 = Bomba-Opoń | first3 = D. | last4 = Horosz | first4 = E. | last5 = Marczewska | first5 = M. | last6 = Wielgoś | first6 = M. | title = Glassy cell carcinoma of the cervix--a case report with review of the literature. | journal = Ginekol Pol | volume = 82 | issue = 12 | pages = 936-9 | month = Dec | year = 2011 | doi =  | PMID = 22384631 }}</ref>
 
===Microscopic===
Features:
*Morphologic features of both squamous carcinoma and adenocarcinoma:
**Adenocarcinoma: gland forming ''or'' mucin vacuoles.
**[[Squamous carcinoma]]: abundant eosinophilic cytoplasm, central nucleus.
 
====Images====
<gallery>
Image:Adenosquamous_carcinoma_intermed_mag.jpg | Adenosquamous carcinoma - intermed. mag. (WC)
Image:Adenosquamous_carcinoma_high_mag.jpg | Adenosquamous carcinoma - high mag. (WC)
</gallery>


==Clear cell carcinoma of the uterine cervix==
==Clear cell carcinoma of the uterine cervix==
*[[AKA]] ''cervical clear cell carcinoma''.
{{Main|Clear cell carcinoma of the uterine cervix}}
===General===
*Associated with ''diethylstilbestrol'' exposure ''in utero''.<ref name=pmid19857300>{{Cite journal  | last1 = van Dijck | first1 = JA. | last2 = Doorduijn | first2 = Y. | last3 = Bulten | first3 = JH. | last4 = Verloop | first4 = J. | last5 = Massuger | first5 = LF. | last6 = Kiemeney | first6 = BA. | title = [Vaginal and cervical cancer due to diethylstilbestrol (DES); end epidemic] | journal = Ned Tijdschr Geneeskd | volume = 153 | issue =  | pages = A366 | month =  | year = 2009 | doi =  | PMID = 19857300 }}</ref>
*Less common in the cervix - when compared to other gynecologic sites.<ref name=Ref_WMSP442>{{Ref WMSP|442}}</ref>
**More common in the [[clear cell carcinoma of the endometrium|endometrium]].<ref>{{Cite journal  | last1 = Babić | first1 = D. | last2 = Kos | first2 = M. | last3 = Jukić | first3 = S. | last4 = Ilić | first4 = J. | last5 = Vecek | first5 = N. | last6 = Kos | first6 = M. | last7 = Mahnik | first7 = N. | title = [Clear cell carcinoma of the female genital tract]. | journal = Jugosl Ginekol Perinatol | volume = 31 | issue = 3-4 | pages = 102-4 | month =  | year =  | doi =  | PMID = 1749271 }}</ref>
 
Note:
*[[HPV]] does '''not''' appear to be important in the oncogenesis;<ref name=pmid21620450>{{Cite journal  | last1 = Kocken | first1 = M. | last2 = Baalbergen | first2 = A. | last3 = Snijders | first3 = PJ. | last4 = Bulten | first4 = J. | last5 = Quint | first5 = WG. | last6 = Smedts | first6 = F. | last7 = Meijer | first7 = CJ. | last8 = Helmerhorst | first8 = TJ. | title = High-risk human papillomavirus seems not involved in DES-related and of limited importance in nonDES related clear-cell carcinoma of the cervix. | journal = Gynecol Oncol | volume = 122 | issue = 2 | pages = 297-302 | month = Aug | year = 2011 | doi = 10.1016/j.ygyno.2011.05.002 | PMID = 21620450 }}</ref> however, this is not completely settled.<ref name=pmid22885379/>
 
===Microscopic===
Features:<ref name=pmid22885379/>
*Like [[clear cell carcinoma]] elsewhere:
**Clear cytoplasm - '''key feature'''.
***May be absent!
**Cells have large free/luminal surface area (hobnailing pattern) and small non-free surface.
**Moderate-to-severe [[nuclear pleomorphism]].
**Tubular and/or cystic morphology.
***May be (simple) papillary and/or solid.
*Adenosis - typically adjacent.
 
DDx:
*[[Clear cell carcinoma of the endometrium]] - diagnosis based on clinico-radiologic correlation (IHC & histology not useful).<ref name=pmid22885379>{{Cite journal  | last1 = Offman | first1 = SL. | last2 = Longacre | first2 = TA. | title = Clear cell carcinoma of the female genital tract (not everything is as clear as it seems). | journal = Adv Anat Pathol | volume = 19 | issue = 5 | pages = 296-312 | month = Sep | year = 2012 | doi = 10.1097/PAP.0b013e31826663b1 | PMID = 22885379 }}</ref>
*[[Serous carcinoma of the endometrium]].
*[[Serous carcinoma of the uterine cervix]].
 
===IHC===
*Essentially considered to be like ''[[endometrial clear cell carcinoma]]''.<ref name=pmid22885379/>


==Small cell carcinoma of the cervix==
==Small cell carcinoma of the cervix==
Line 975: Line 537:


==Glassy cell carcinoma==
==Glassy cell carcinoma==
===General===
{{Main|Glassy cell carcinoma}}
*Rare.
*Rapid growth, poor prognosis.<ref name=pmid19527406>{{Cite journal  | last1 = Nasu | first1 = K. | last2 = Takai | first2 = N. | last3 = Narahara | first3 = H. | title = Multimodal treatment for glassy cell carcinoma of the uterine cervix. | journal = J Obstet Gynaecol Res | volume = 35 | issue = 3 | pages = 584-7 | month = Jun | year = 2009 | doi = 10.1111/j.1447-0756.2008.00968.x | PMID = 19527406 }}</ref>
*Considered a subtype of [[adenosquamous carcinoma]].<ref name=pmid22384631>{{Cite journal  | last1 = Kosińiska-Kaczyńska | first1 = K. | last2 = Mazanowska | first2 = N. | last3 = Bomba-Opoń | first3 = D. | last4 = Horosz | first4 = E. | last5 = Marczewska | first5 = M. | last6 = Wielgoś | first6 = M. | title = Glassy cell carcinoma of the cervix--a case report with review of the literature. | journal = Ginekol Pol | volume = 82 | issue = 12 | pages = 936-9 | month = Dec | year = 2011 | doi =  | PMID = 22384631 }}</ref>
 
===Microscopic===
Features:<ref name=pmid11393075>{{Cite journal  | last1 = Reis-Filho | first1 = JS. | last2 = Fillus Neto | first2 = J. | last3 = Schonemann | first3 = E. | last4 = Sanderson | first4 = A. | last5 = Schmitt | first5 = FC. | title = Glassy cell carcinoma of the uterine cervix. Report of a case with cytohistologic and immunohistochemical study. | journal = Acta Cytol | volume = 45 | issue = 3 | pages = 407-10 | month =  | year =  | doi =  | PMID = 11393075 }}</ref>
*Epithelioid cells in sheets or cords.
*Round/oval nucleus.
*One or more prominent nucleoli.
*Abundant finely vacuolated eosinophilic to amphophilic cytoplasm.
*Distinct cell borders.
*Inflammation - esp. eosinophils.<ref>URL: [http://www.webpathology.com/image.asp?n=2&Case=561 http://www.webpathology.com/image.asp?n=2&Case=561]. Accessed on: 4 September 2011.</ref>
 
DDx:
*[[Adenosquamous carcinoma of the uterine cervix]].
*[[Squamous carcinoma of the uterine cervix]].
 
Images:
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Glassy_cell_carcinoma_-_low_mag.jpg GCC - low mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Glassy_cell_carcinoma_-_high_mag.jpg GCC - high mag. (WC)].
*www:
**[http://www.webpathology.com/image.asp?n=1&Case=561 GCC - low mag. (webpathology.com)].
**[http://www.webpathology.com/image.asp?n=2&Case=561 GCC - high mag. (webpathology.com)].
**[http://path.upmc.edu/cases/case100/dx.html GCC - several images (upmc.edu)].
 
===Stains===
*[[PAS stain]] - marks plasma membrane.<ref name=pmid15318016>{{Cite journal  | last1 = Deshpande | first1 = AH. | last2 = Kotwal | first2 = MN. | last3 = Bobhate | first3 = SK. | title = Glassy cell carcinoma of the uterine cervix a rare histology. Report of three cases with a review of the literature. | journal = Indian J Cancer | volume = 41 | issue = 2 | pages = 92-5 | month =  | year =  | doi =  | PMID = 15318016 | URL = http://www.indianjcancer.com/text.asp?2004/41/2/92/12353}}</ref>


==Villoglandular adenocarcinoma of the cervix==
==Villoglandular adenocarcinoma of the cervix==
Line 1,024: Line 558:
*Serous carcinoma of the cervix.
*Serous carcinoma of the cervix.


Images:
====Images====
*www:
www:
**[http://www.webpathology.com/image.asp?n=11&Case=560 VGA (webpathology.com)].
*[http://www.webpathology.com/image.asp?n=11&Case=560 VGA (webpathology.com)].
*[[WC]]:
<gallery>
**[http://commons.wikimedia.org/wiki/File:Villoglandular_adenocarcinoma_-_very_low_mag.jpg VGA - very low mag. (WC)].
Image:Villoglandular_adenocarcinoma_-_very_low_mag.jpg | VGA - very low mag. (WC)
**[http://commons.wikimedia.org/wiki/File:Villoglandular_adenocarcinoma_-_intermed_mag.jpg VGA - intermed. mag. (WC)].
Image:Villoglandular_adenocarcinoma_-_intermed_mag.jpg | VGA - intermed. mag. (WC)
**[http://commons.wikimedia.org/wiki/File:Villoglandular_adenocarcinoma_-_very_high_mag.jpg VGA - very high mag. (WC)].
Image:Villoglandular_adenocarcinoma_-_very_high_mag.jpg | VGA - very high mag. (WC)
</gallery>


==Mucoepidermoid carcinoma of the uterine cervix==
==Mucoepidermoid carcinoma of the uterine cervix==
Line 1,064: Line 599:


==Mesonephric adenocarcinoma==
==Mesonephric adenocarcinoma==
===General===
{{Main|Mesonephric adenocarcinoma}}
*Arises from the [[mesonephric duct remnants]].
 
===Microscopic===
Features:<ref name=Ref_WMSP442>{{Ref WMSP|442}}</ref>
*Nuclear atypia - '''key feature'''.
**Nuclear crowding.
*Variable architecture:
**Tubular, papillary, solid, retiform (net-like<ref>URL: [http://www.thefreedictionary.com/retiform http://www.thefreedictionary.com/retiform]. Accessed on: 25 August 2012.</ref>).
 
DDx:
*[[Mesonephric duct remnants]].
*[[Cervical adenocarcinoma]].
*[[Colorectal adenocarcinoma]].
*Endometrioid adenocarcinoma.
 
===IHC===
Features:<ref name=Ref_WMSP442>{{Ref WMSP|442}}</ref>
*CK7 +ve.
*CD10 +ve.
 
Others:<ref name=Ref_WMSP442>{{Ref WMSP|442}}</ref>
*CK20 -ve.
*ER -ve.
*PR -ve.
*CEA -ve.


==Minimal deviation adenocarcinoma of the uterine cervix==
==Minimal deviation adenocarcinoma of the uterine cervix==
*[[AKA]] ''adenoma malignum''.
*[[AKA]] ''adenoma malignum''.
*[[AKA]] ''minimal deviation adenocarcinoma'', abbreviated ''MDA''.
*[[AKA]] ''minimal deviation adenocarcinoma'', abbreviated ''MDA''.
===General===
{{Main|Minimal deviation adenocarcinoma of the uterine cervix}}
*Rare and difficult diagnosis.<ref name=pmid12828609>{{Cite journal  | last1 = Tsuda | first1 = H. | last2 = Mikami | first2 = Y. | last3 = Kaku | first3 = T. | last4 = Akiyama | first4 = F. | last5 = Hasegawa | first5 = T. | last6 = Okada | first6 = S. | last7 = Hayashi | first7 = I. | last8 = Kasamatsu | first8 = T. | title = Interobserver variation in the diagnosis of adenoma malignum (minimal deviation adenocarcinoma) of the uterine cervix. | journal = Pathol Int | volume = 53 | issue = 7 | pages = 440-9 | month = Jul | year = 2003 | doi =  | PMID = 12828609 }}</ref>
**Requires a deep sampling;<ref name=pmid22385609>{{Cite journal  | last1 = Lim | first1 = KT. | last2 = Lee | first2 = IH. | last3 = Kim | first3 = TJ. | last4 = Kwon | first4 = YS. | last5 = Jeong | first5 = JG. | last6 = Shin | first6 = SJ. | title = Adenoma malignum of the uterine cervix: Clinicopathologic analysis of 18 cases. | journal = Kaohsiung J Med Sci | volume = 28 | issue = 3 | pages = 161-4 | month = Mar | year = 2012 | doi = 10.1016/j.kjms.2011.10.009 | PMID = 22385609 }}</ref> thus,  usually diagnosed on cone biopsy or hysterectomy.
*Associated with [[Peutz-Jeghers syndrome]].<ref name=pmid21503748>{{Cite journal  | last1 = Riegert-Johnson | first1 = D. | last2 = Roberts | first2 = M. | last3 = Gleeson | first3 = FC. | last4 = Krishna | first4 = M. | last5 = Boardman | first5 = L. | title = Case studies in the diagnosis and management of Peutz-Jeghers syndrome. | journal = Fam Cancer | volume = 10 | issue = 3 | pages = 463-8 | month = Sep | year = 2011 | doi = 10.1007/s10689-011-9438-x | PMID = 21503748 }}</ref><ref name=pmid22878090>{{Cite journal  | last1 = Ito | first1 = M. | last2 = Minamiguchi | first2 = S. | last3 = Mikami | first3 = Y. | last4 = Ueda | first4 = Y. | last5 = Sekiyama | first5 = K. | last6 = Yamamoto | first6 = T. | last7 = Takakura | first7 = K. | title = Peutz-Jeghers syndrome-associated atypical mucinous proliferation of the uterine cervix: A case of minimal deviation adenocarcinoma ('adenoma malignum') in situ. | journal = Pathol Res Pract | volume =  | issue =  | pages =  | month = Aug | year = 2012 | doi = 10.1016/j.prp.2012.06.008 | PMID = 22878090 }}</ref>
*Poor prognosis.<ref name=pmid2764221>{{Cite journal  | last1 = Gilks | first1 = CB. | last2 = Young | first2 = RH. | last3 = Aguirre | first3 = P. | last4 = DeLellis | first4 = RA. | last5 = Scully | first5 = RE. | title = Adenoma malignum (minimal deviation adenocarcinoma) of the uterine cervix. A clinicopathological and immunohistochemical analysis of 26 cases. | journal = Am J Surg Pathol | volume = 13 | issue = 9 | pages = 717-29 | month = Sep | year = 1989 | doi =  | PMID = 2764221 }}</ref>
 
===Microscopic===
Features:<ref name=Ref_WMSP441-2>{{Ref WMSP|441-2}}</ref>
*Deep infiltrating glands - '''key feature'''.
**Desmoplastic stroma - may be subtle.
**Perivascular and/or perineural location.
*Minimal nuclear atypia.
*Abnormal gland morphology<ref name=pmid2764221/> / loss of lobular (gland) architecture. †
 
Note:
*† '''Not''' a criterion required by all pathologists.<ref name=pmid12828609/>
 
DDx:<ref name=pmid12828609/>
*[[Adenocarcinoma of the uterine cervix]] - has "obvious" nuclear atypia.
*[[Tunnel cluster]].
 
===IHC===
Features:
*CEA +ve.<ref name=pmid2764221/>
*p16 -ve.{{fact}}


=See also=
=See also=
Line 1,131: Line 617:
=External links=
=External links=
*[http://www.medecine.ups-tlse.fr/dcem1/histologie/courtade/CINtec.pdf Interpretation altas for p16 staining (ups-tlse.fr)].
*[http://www.medecine.ups-tlse.fr/dcem1/histologie/courtade/CINtec.pdf Interpretation altas for p16 staining (ups-tlse.fr)].
*[http://www.glowm.com/section_view/heading/Pathology%20of%20Cervical%20Carcinoma/item/230#26011 Cervical carcinoma (glowm.com)].
*[http://www.obgyn.net/gynecological-oncology/electrosurgery-cervical-intraepithelial-neoplasia Treatments for CIN (obgyn.net)].


[[Category:Gynecologic pathology]]
[[Category:Gynecologic pathology]]
Michael
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