Difference between revisions of "Uterine cervix"

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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:
Images:
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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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#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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*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==
*Abbreviated ''SMC''.
*Abbreviated ''SMC''.
===General===
{{Main|Squamous metaplasia of the uterine cervix}}
*Benign process: columnar cells -> squamoid cells.
**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.
* Adjacent/closely associated with columnar epithelium.
** Columnar epithelium superficial in immature metaplasia.
 
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.
*May have goblet cells - uncommon.<ref name=pmid21077478>{{Cite journal  | last1 = Sivridis | first1 = E. | last2 = Karpathiou | first2 = G. | last3 = Malamou-Mitsi | first3 = V. | last4 = Giatromanolaki | first4 = A. | title = Intestinal-type metaplasia in the original squamous epithelium of the cervix. | journal = Eur J Gynaecol Oncol | volume = 31 | issue = 3 | pages = 319-22 | month =  | year = 2010 | doi =  | PMID = 21077478 }}</ref>
 
DDx:
*[[CIN II]] - esp. for immature squamous metaplasia.
*[[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)].
*[http://www.eurocytology.eu/static/eurocytology/eng/cervical/mod1img4b.html Immature squamous metaplasia (eurocytology.eu)].<ref>URL: [http://www.eurocytology.eu/static/eurocytology/eng/cervical/LP1ContentAcontD.html http://www.eurocytology.eu/static/eurocytology/eng/cervical/LP1ContentAcontD.html]. Accessed on: 9 October 2013.</ref>
 
===IHC===
*p16 weak-to-moderate patchy +ve -- checkerboard-like; not full thickness.
**Strong diffuse full thickness positivity in HSIL and SCC.
*Ki-67 - low proliferative rate.
 
===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===
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===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}}
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*[[AKA]] ''atrophy of the cervix''.
*[[AKA]] ''atrophy of the cervix''.
*[[AKA]] ''cervix with atrophic changes''.
*[[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===
*Uncommon.
*Clinical history: radiation treatment for cervical carcinoma.<ref name=pmid2209348/>
===Microscopic===
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>
*Nuclear enlargement with a normal [[NC ratio]].
*+/-Coarse chromatin.
*+/-Nucleoli.
*+/-Multinucleation - very common.
*Histiocytes - common.
==Reactive endocervical cells==
===General===
===General===
*Common.
*Benign.
*Post-menupausal.
*Important to recognize and differentiate from [[HSIL]].


===Microscopic===
===Microscopic===
Features:
Features:
*Cells smaller.
*Mild nuclear enlargement.
*Cytoplasm grey/blue.
*+/-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>
*No "dancing"/"sparkling" chromatin.
*No mitoses.


DDx:
Notes:
*[[HSIL]].
DDx of multinucleated endocervical cells:  
*[[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>
*Benign endocervical cells.


====Images====
====Images====
<gallery>
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>
www:
www:
*[http://nih.techriver.net/view.php?patientId=93 Atrophic cervix (nih.techriver.net)].
*[http://www.surgpath4u.com/caseviewer.php?case_no=229 Reactive endocervical cells (surgpath4u.com)].
*[http://www.flickriver.com/photos/euthman/3884912676/ Atrophic cervix (flickriver.com/euthman)].
*[http://www.eurocytology.eu/static/eurocytology/image/mod1newa.jpg Atrophic changes in the vagina (eurocytology.eu)].<ref>URL: [http://www.eurocytology.eu/static/eurocytology/TUR/cervical/LP1ContentLcontC.html http://www.eurocytology.eu/static/eurocytology/TUR/cervical/LP1ContentLcontC.html]. Accessed on: 13 December 2013.</ref>
 
===IHC===
*p16 -ve.
*Ki-67 rare basal cells.
 
===Sign out===
<pre>
UTERINE CERVIX, BIOPSY:
- SQUAMOUS MUCOSA WITH ATROPHIC CHANGES.
- BENIGN ENDOCERVICAL EPITHELIUM.
- NEGATIVE FOR DYSPLASIA.
 
COMMENT:
A p16 immunostain is negative. A Ki-67 immunostain marks rare basal cells.
</pre>


=Non-invasive=
=Non-invasive=
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:''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.
*[[Proliferative phase endometrium]] - endometrial type stroma, cytoplasm not pale staining, no nuclear atypia (smooth nuclear contour, stratified).
 
Images:
*[http://www.flickriver.com/photos/euthman/tags/cervix/ Endocervical AIS adjacent to normal (flickriver.com/euthman)].
*[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 605: 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 769: 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 845: 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 894: 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 934: 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 1,002: Line 618:
*[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.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]]

Latest revision as of 18:31, 17 November 2021

The uterine cervix, also simply cervix, is the gateway to the uterine corpus. It is not infrequently afflicted by cancer -- squamous cell carcinoma. Prior to routine Pap tests it was a leading cause of cancer death in women in the Western world.

Polyps associated with the cervix are discussed the cervical polyp article.

Cytopathology of the uterine cervix is dealt with in the gynecologic cytopathology article.

Introduction

Overview

  • Most cervix cancer is squamous cell carcinoma.
  • The work-up of a suspicious Pap test is a colposcopic examination and biopsies, which are the topic of this article.

Indications for coloposcopic exam (based on the ASCCP Consensus Guidelines of 2001):[1]

Colposcopic examination

  • Performed by gynecologists.
  • Exam usually includes a search for acetowhite epithelium (AWE); this is accomplished by the application of acetic acid (to help identify lesions for biopsy).
  • Cervical ectropian (AKA cervical eversion, AKA ectropian) = endocervical epithelium at external os, considered benign, grossly has a granulation tissue-like appearance.[4]

Cervical specimens

Cytology

Biopsies

The types of biopsies that are done are:

  1. Cervical biopsies - prompted by abnormal Pap test, e.g. HSIL, to look for squamous cell carcinoma of the uterine cervix.
  2. Endocervical curettage (ECC) - to work-up columnar dysplasia, e.g. endocervical adenocarcinoma/endometrial adenocarcinoma.

Surgical specimens

  1. Loop electrosurgical excision procedure (LEEP).
    • AKA large loop excision of the transformation zone (LLETZ).[5][6]
  2. Radical trachelectomy - removal of the uterine cervix and parametria, preserves fertility.
  3. Radical hysterectomy - advanced cervical carcinoma (Stage IA2 and Stage IB1), recurrent carcinoma.[7]

Other

Normal histology

Features:

  • 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".[8]
    • Also known as "transition zone".

Notes:

  • Considered from the perspective of histology:
    • The squamous component is referred to as the exocervix (or ectocervix[9]).
    • The simple columnar (or glandular) component is referred to as the endocervix.

Images:

Negative LEEP

Main article: LEEP

Transformation zone - biopsy

Microscopic

Features:

  • Small round cells.
  • Usually no halos.
    • May be seen in pseudokoilocytes.
  • No nuclear membrane irregularities.
  • No nuclear hyperchromasia.

Images

  • NILM with pseudokoilocytes - intermed. mag. (WC)

  • NILM with pseudokoilocytes - high mag. (WC)

  • NILM with pseudokoilocytes - very high mag. (WC)

  • Benign stripped exocervix - high mag. (WC)

www:

Sign out

UTERINE CERVIX, BIOPSY: 
- TRANSFORMATION ZONE WITHOUT APPARENT PATHOLOGY.
- NEGATIVE FOR DYSPLASIA.

UTERINE CERVIX, BIOPSY:
- SQUAMOUS MUCOSA WITHOUT APPARENT PATHOLOGY.
- STRIPPED ENDOCERVICAL EPITHELIUM WITHOUT APPARENT PATHOLOGY.
- NEGATIVE FOR DYSPLASIA.

Endocervical glands

Microscopic

Features: Cervical glands normally have round nuclei and vaguely resemble the colonic mucosa.

Notes:

  • If the nuclei are columnar think cancer! This is like in the colon-- columnar nuclei = badness.
    • Memory device: The Cs (Cervix & Colon) are similar.
  • Endocervical epithelium (ECE) has a morphology similar to the epithelium of secretory phase endometrium (SPE):
    • ECE - grey foamy appearing cytoplasm.
    • SPE - eosinophilic cytoplasm.
      • Most useful feature to differentiate ECE and SPE is the accompanying stroma.

Sign out

UTERINE ENDOCERVIX, CURETTAGE: 
- ENDOCERVICAL MUCOSA AND STRIPPED ENDOCERVICAL EPITHELIUM WITHIN NORMAL LIMITS.

Inflamed with squamous epithelium

UTERINE ENDOCERVIX, CURETTAGE:
- BENIGN STRIPPED ENDOCERVICAL EPITHELIUM AND SCANT INFLAMED ENDOCERVICAL MUCOSA.
- VERY SCANT SUPERFICIAL SQUAMOUS EPITHELIUM WITHOUT APPARENT PATHOLOGY.

Squamous epithelium present

UTERINE ENDOCERVIX, CURETTAGE: 
- ENDOCERVICAL MUCOSA WITHIN NORMAL LIMITS. 
- SQUAMOUS EPITHELIUM WITHOUT APPARENT PATHOLOGY.

Endometrium present

UTERINE ENDOCERVIX, CURETTAGE: 
- ENDOCERVICAL MUCOSA WITHIN NORMAL LIMITS. 
- SCANT NON-PROLIFERATIVE ENDOMETRIUM.

Inflamed

UTERINE ENDOCERVIX, CURETTAGE: 
- INFLAMED ENDOCERVICAL MUCOSA. 
- REACTIVE SQUAMOUS EPITHELIUM.
- NEGATIVE FOR MALIGNANCY.

UTERINE ENDOCERVIX, CURETTAGE:
- BENIGN INFLAMED ENDOCERVICAL MUCOSA.
- STRIPPED ENDOCERVICAL EPITHELIUM WITHIN NORMAL LIMITS.

No stroma present

UTERINE ENDOCERVIX, CURETTAGE: 
- STRIPPED ENDOCERVICAL EPITHELIUM WITHOUT APPARENT PATHOLOGY.

Limited tissue

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.

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. Clinical correlation is
suggested.

UTERINE ENDOCERVIX, CURETTAGE:
- BENIGN SQUAMOUS EPITHELIUM WITH METAPLASTIC CHANGE.
- VERY SCANT BENIGN ENDOCERVICAL EPITHELIUM, SUBOPTIMAL SAMPLING.

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.

Inadequate biopsy

  • Unfortunately, inadequate biopsies are common.

Endocervix

Sign out

No endocervical epithelium

UTERINE ENDOCERVIX, CURETTAGE: 
- SQUAMOUS EPITHELIUM WITHOUT APPARENT PATHOLOGY.
- NO ENDOCERVICAL EPITHELIUM IDENTIFIED.
- MUCOUS AND INFLAMMATORY CELLS.

No epithelium

UTERINE ENDOCERVIX, CURETTAGE: 
- MUCOUS AND INFLAMMATORY CELLS.
- NO EPITHELIUM IDENTIFIED.

No tissue

UTERINE ENDOCERVIX, CURETTAGE: 
- NO TISSUE PRESENT, SEE COMMENT. 

COMMENT: 
No tissue identified on gross or microscopy.

UTERINE ENDOCERVIX, CURETTAGE:
- NO TISSUE PRESENT, SEE COMMENT.

COMMENT:
No tissue identified on microscopy. No tissue is seen on inspection of the paraffin block.

Where to start

  1. Identify epithelium - exocervical (stratified squamous), endocervical (simple columnar), both.
    • If there is both exocervix and endocervix --> transition zone.
  2. Identify possible squamous lesions.
  3. Identify possible endocervical lesions.

Benign entities of the cervix

The cervix is MANTLED:

Benign

Nabothian cyst

General

  • Benign.
  • Common.

Gross

  • Bump.
  • Pale colour.

DDx - clinical:

Image

  • Nabothian cyst. (WC/euthman)

Microscopic

Features:

  • Simple endocervical cyst.
    • Usually lined by endocervical epithelial cells - may be flattened.
      • Columnar morphology with large clear, apical vacuoles.
    • +/-Macrophages.
    • +/-Mucus.

Note:

Image:

Sign out

CERVICAL POLYP, REMOVAL:
- BENIGN POLYPOID FRAGMENT OF EXOCERVICAL MUCOSA WITH NABOTHIAN CYSTS AND 
BENIGN ENDOCERVICAL EPITHELIUM.

POLYPOID LESION ("CERVICAL POLYP"), EXCISION:
- POLYPOID NABOTHIAN CYST.

Tunnel cluster

General

Microscopic

Features:[13][14]

  • Well-circumscribed lesion consisting of:
  • Benign endocervical glands.
    • Dilated & filled with mucin or (less commonly) eosinophilic secretions.
    • Lining epithelium compressed/flattened (attenuated).
    • Gland architecture: branching, tortuous.
    • Scant intervening stroma.

Notes:

  1. Usually no nuclear atypia and no mitotic activity.
  2. Important only as one could possibly mistake it as minimal deviation adenocarcinoma, AKA adenoma malignum.[15]

Images

  • Tunnel cluster - very low mag. (WC)

  • Tunnel cluster - low mag. (WC)

  • Tunnel cluster - intermed. mag. (WC)

  • Tunnel cluster - high mag. (WC)

  • Tunnel cluster - very high mag. (WC)

www:

Microglandular hyperplasia

Not to be confused with microglandular adenosis.
  • Abbreviated MGH.
  • AKA microglandular change.
Main article: Microglandular hyperplasia

Wolffian duct hyperplasia

General

  • Benign.

Microscopic

Features:

  • Abundant small tubules with a simple cuboidal epithelium.
  • Round small bland nucleus.

DDx:

Stains

Squamous metaplasia of the uterine cervix

  • Abbreviated SMC.
Main article: Squamous metaplasia of the uterine cervix

Reactive squamous epithelium of the uterine cervix

  • AKA reactive squamous epithelium.
  • AKA reactive changes.

General

  • Common.
  • Individuals with persistent inflammation on Pap test may have occult SIL.[16]

Microscopic

Features:

  1. Inflammation - key feature.
    • Lymphocytes.
    • Plasma cells.
  2. Mild nuclear enlargement. †
  3. Nucleoli - important.

Note:

  • † Normal squamous cell nuclei are approximately 8 μm.[17]
    • Mild enlargement ~ 2-3x normal.
    • CIN I nuclei are ~ 3x normal (24 μm).

DDx:

IHC

  • p16 -ve.

Sign out

UTERINE CERVIX, BIOPSY:
- REACTIVE SQUAMOUS EPITHELIUM.
- BENIGN ENDOCERVICAL GLANDS.
- NEGATIVE FOR MALIGNANCY.

COMMENT:
The squamous epithelium is negative for p16 staining. Ki-67 staining is predominantly in
the lower third of the epithelium.

Tubal metaplasia of the uterine cervix

  • AKA tubal metaplasia, abbreviated TM.

General

  • Benign.
  • Mimics the appearance of AIS - especially at low power.

Microscopic

Features - like the fallopian tube:

  • Nuclear crowding vis-à-vis benign endocervical epithelium (low power).
  • Mixed cell population (high power):
    • Peg cells - "tall" and "skinny".
      • Columnar/golf tee-like appearance.
    • Ciliated cells - cilia, pale cytoplasm, round central nucleus.
    • Secretory cells - non-ciliated, basophilic cytoplasm, round small basal nuclei.

DDx:

Image:

IHC

Features:[18]

Atrophy of the uterine cervix

  • AKA cervical atrophy.
  • AKA atrophy of the cervix.
  • AKA cervix with atrophic changes.
Main article: Uterine cervix with atrophic changes

Radiation changes of the endocervical epithelium

Main article: Radiation changes
Main article: Radiation changes in cervical cytology

General

  • Uncommon.
  • Clinical history: radiation treatment for cervical carcinoma.[19]

Microscopic

Features:[19]

  • Nuclear enlargement with a normal NC ratio.
  • +/-Coarse chromatin.
  • +/-Nucleoli.
  • +/-Multinucleation - very common.
  • Histiocytes - common.

Reactive endocervical cells

General

  • Benign.

Microscopic

Features:

  • Mild nuclear enlargement.
  • +/-Multinucleation.[20]

Notes: DDx of multinucleated endocervical cells:

  • HSV.[21]
  • Benign endocervical cells.

Images

  • Multinucleated endocervix - high mag.

  • Multinucleated endocervix - very high mag.

  • Multinucleated endocervix - extremely high mag.

www:

Non-invasive

Cervical intraepithelial neoplasia

  • Previously known as cervical intraepithelial neoplasia and cervical dysplasia.
Main article: Squamous intraepithelial lesion of the uterine cervix

Endocervical adenocarcinoma in situ

For the cytology see Gynecologic cytopathology#Endocervical adenocarcinoma in situ
  • AKA adenocarcinoma in situ, abbreviated AIS.
Main article: Endocervical adenocarcinoma in situ

Cancer

Squamous cell carcinoma of the uterine cervix

Main article: Squamous cell carcinoma
  • AKA cervical squamous cell carcinoma.
Main article: Squamous cell carcinoma of the uterine cervix

Adenocarcinoma of the uterine cervix

  • AKA endocervical adenocarcinoma.
  • AKA cervical adenocarcinoma.
Main article: Adenocarcinoma of the uterine cervix

Uncommon non-invasive

Stratified mucin-producing intraepithelial lesions of the cervix

  • Abbreviated SMILE (Stratified Mucin-producing Intraepithelial LEsion).
Main article: Stratified mucin-producing intraepithelial lesion of the cervix

Uncommon types of cervical cancer

There are a number of uncommon type of cervical cancer.

Serous carcinoma of the uterine cervix

General

  • Poor prognosis.[22]
  • Extremely rare.

Microscopic

Features:

Adenosquamous carcinoma of the uterine cervix

Main article: Adenosquamous carcinoma of the uterine cervix

Clear cell carcinoma of the uterine cervix

Main article: Clear cell carcinoma of the uterine cervix

Small cell carcinoma of the cervix

Main article: Small cell carcinoma
  • Like small cell carcinoma elsewhere.

DDx:

IHC

  • HPV +ve.

Adenoid basal carcinoma

See also: Basal cell carcinoma.

General

Microscopic

Features:[23]

  • Nests of cells with basaloid rim and squamoid center.
    • Basaloid cells look benign.

DDx:

Image:

Glassy cell carcinoma

Main article: Glassy cell carcinoma

Villoglandular adenocarcinoma of the cervix

  • AKA well-differentiated papillary villoglandular adenocarcinoma,[24] AKA villoglandular papillary adenocarcinoma, AKA well-differentiated villoglandular adenocarcinoma.

General

  • Rare.
  • Younger patients and relatively good prognosis.[25]
  • Associated with HPV.
  • May also arise from the endometrium.[26]

Microscopic

Features:[27]

  • Papillary structures (nipple-like shapes with a fibrovascular core) that are long.
    • Nobody defines "long".
      • Perhaps - long >3:1 length:width.
  • Covered by columnar (or cuboidal) epithelium.
  • Intracellular mucin (focal).

DDx:

  • Serous carcinoma of the cervix.

Images

www:

  • VGA - very low mag. (WC)

  • VGA - intermed. mag. (WC)

  • VGA - very high mag. (WC)

Mucoepidermoid carcinoma of the uterine cervix

Main article: Mucoepidermoid carcinoma

General

  • Controversial - not in the WHO.[28]

Microscopic

Features:[29]

  • Squamous cell carcinoma-like with:
    1. No glands formation.
    2. Intracellular mucin.
      • Classically have mucous cells - cells with abundant fluffy cytoplasm and large mucin vacuoles - key feature.

Notes:

DDx:

Stains

Mucin stains:[29]

IHC

Molecular

Like the salivary gland tumour:

  • t(11;19) CRTC1/MAML2.[28]

Mesonephric adenocarcinoma

Main article: Mesonephric adenocarcinoma

Minimal deviation adenocarcinoma of the uterine cervix

  • AKA adenoma malignum.
  • AKA minimal deviation adenocarcinoma, abbreviated MDA.
Main article: Minimal deviation adenocarcinoma of the uterine cervix

See also

References

  1. ↑ Dresang, LT.. "Colposcopy: an evidence-based update.". J Am Board Fam Pract 18 (5): 383-92. PMID 16148248.
  2. ↑ Zonios, G. (Aug 2012). "Reflectance model for acetowhite epithelium.". J Biomed Opt 17 (8): 87003-1. doi:10.1117/1.JBO.17.8.087003. PMID 23224202.
  3. ↑ Li, W.; Venkataraman, S.; Gustafsson, U.; Oyama, JC.; Ferris, DG.; Lieberman, RW.. "Using acetowhite opacity index for detecting cervical intraepithelial neoplasia.". J Biomed Opt 14 (1): 014020. doi:10.1117/1.3079810. PMID 19256708.
  4. ↑ Casey, PM.; Long, ME.; Marnach, ML. (Feb 2011). "Abnormal cervical appearance: what to do, when to worry?". Mayo Clin Proc 86 (2): 147-50; quiz 151. doi:10.4065/mcp.2010.0512. PMC 3031439. PMID 21270291. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031439/.
  5. ↑ Kenwright, D.; Braam, G.; Maharaj, D.; Langdana, F. (Jan 2012). "Multiple levels on LLETZ biopsies do not contribute to patient management.". Pathology 44 (1): 7-10. doi:10.1097/PAT.0b013e32834d7b5d. PMID 22173237.
  6. ↑ URL: http://www.webmd.com/cancer/cervical-cancer/loop-electrosurgical-excision-procedure-leep-for-abnormal-cervical-cell-changes. Accessed on: 20 March 2014.
  7. ↑ Ware, RA.; van Nagell, JR. (2010). "Radical hysterectomy with pelvic lymphadenectomy: indications, technique, and complications.". Obstet Gynecol Int 2010. doi:10.1155/2010/587610. PMID 20871657.
  8. ↑ URL: http://www.med-ed.virginia.edu/Courses/path/gyn/cervix1.cfm. Accessed on: 12 May 2010.
  9. ↑ URL: http://www.cancer.org/cancer/cervicalcancer/detailedguide/cervical-cancer-what-is-cervical-cancer. Accessed on: 27 January 2014.
  10. ↑ Nucci, MR. (Oct 2002). "Symposium part III: tumor-like glandular lesions of the uterine cervix.". Int J Gynecol Pathol 21 (4): 347-59. PMID 12352183.
  11. ↑ Zaino, RJ. (Mar 2000). "Glandular lesions of the uterine cervix.". Mod Pathol 13 (3): 261-74. doi:10.1038/modpathol.3880047. PMID 10757337.
  12. ↑ Okamoto, Y.; Tanaka, YO.; Nishida, M.; Tsunoda, H.; Yoshikawa, H.; Itai, Y.. "MR imaging of the uterine cervix: imaging-pathologic correlation.". Radiographics 23 (2): 425-45; quiz 534-5. PMID 12640157.
  13. ↑ URL: http://pathologyoutlines.com/cervix.html#tunnelclusters. Accessed on: 27 February 2011.
  14. ↑ URL: http://surgpath4u.com/caseviewer.php?case_no=477. Accessed on: 5 September 2011.
  15. ↑ Gilks CB, Young RH, Aguirre P, DeLellis RA, Scully RE (September 1989). "Adenoma malignum (minimal deviation adenocarcinoma) of the uterine cervix. A clinicopathological and immunohistochemical analysis of 26 cases". Am. J. Surg. Pathol. 13 (9): 717–29. PMID 2764221.
  16. ↑ Bhutia, K.; Puri, M.; Gami, N.; Aggarwal, K.; Trivedi, SS.. "Persistent inflammation on Pap smear: does it warrant evaluation?". Indian J Cancer 48 (2): 220-2. doi:10.4103/0019-509X.82901. PMID 21768670.
  17. ↑ URL: http://www.curran.pwp.blueyonder.co.uk/cytology.htm. Accessed on: 5 November 2012.
  18. ↑ Marques, T.; Andrade, LA.; Vassallo, J. (Jun 1996). "Endocervical tubal metaplasia and adenocarcinoma in situ: role of immunohistochemistry for carcinoembryonic antigen and vimentin in differential diagnosis.". Histopathology 28 (6): 549-50. PMID 8803599.
  19. ↑ 19.0 19.1 Frierson, HF.; Covell, JL.; Andersen, WA. (1990). "Radiation changes in endocervical cells in brush specimens.". Diagn Cytopathol 6 (4): 243-7. PMID 2209348.
  20. ↑ URL: http://www.surgpath4u.com/caseviewer.php?case_no=229. Accessed on: 2 January 2014.
  21. ↑ Naib, ZM.; Nahmias, AJ.; Josey, WE.; Zaki, SA. (Jun 1973). "Relation of cytohistopathology of genital herpesvirus infection to cervical anaplasia.". Cancer Res 33 (6): 1452-63. PMID 4352382.
  22. ↑ Togami, S.; Kasamatsu, T.; Sasajima, Y.; Onda, T.; Ishikawa, M.; Ikeda, S.; Kato, T.; Tsuda, H. (2012). "Serous adenocarcinoma of the uterine cervix: a clinicopathological study of 12 cases and a review of the literature.". Gynecol Obstet Invest 73 (1): 26-31. doi:10.1159/000329319. PMID 21876330.
  23. ↑ 23.0 23.1 Senzaki H, Osaki T, Uemura Y, et al. (December 1997). "Adenoid basal carcinoma of the uterine cervix: immunohistochemical study and literature review". Jpn. J. Clin. Oncol. 27 (6): 437–41. PMID 9438010. http://jjco.oxfordjournals.org/cgi/content/full/27/6/437.
  24. ↑ Fadare, O.; Zheng, W. (Nov 2005). "Well-differentiated papillary villoglandular adenocarcinoma of the uterine cervix with a focal high-grade component: is there a need for reassessment?". Virchows Arch 447 (5): 883-7. doi:10.1007/s00428-005-0030-3. PMID 16088403.
  25. ↑ Korach, J.; Machtinger, R.; Perri, T.; Vicus, D.; Segal, J.; Fridman, E.; Ben-Baruch, G. (2009). "Villoglandular papillary adenocarcinoma of the uterine cervix: a diagnostic challenge.". Acta Obstet Gynecol Scand 88 (3): 355-8. doi:10.1080/00016340902730359. PMID 19172445.
  26. ↑ Zaino, RJ.; Kurman, RJ.; Brunetto, VL.; Morrow, CP.; Bentley, RC.; Cappellari, JO.; Bitterman, P. (Nov 1998). "Villoglandular adenocarcinoma of the endometrium: a clinicopathologic study of 61 cases: a gynecologic oncology group study.". Am J Surg Pathol 22 (11): 1379-85. PMID 9808130.
  27. ↑ Nucci, Marisa R.; Oliva, Esther (2009). Gynecologic Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 180-1. ISBN 978-0443069208.
  28. ↑ 28.0 28.1 28.2 Lennerz, JK.; Perry, A.; Mills, JC.; Huettner, PC.; Pfeifer, JD. (Jun 2009). "Mucoepidermoid carcinoma of the cervix: another tumor with the t(11;19)-associated CRTC1-MAML2 gene fusion.". Am J Surg Pathol 33 (6): 835-43. doi:10.1097/PAS.0b013e318190cf5b. PMID 19092631.
  29. ↑ 29.0 29.1 29.2 Thelmo, WL.; Nicastri, AD.; Fruchter, R.; Spring, H.; DiMaio, T.; Boyce, J. (1990). "Mucoepidermoid carcinoma of uterine cervix stage IB. Long-term follow-up, histochemical and immunohistochemical study.". Int J Gynecol Pathol 9 (4): 316-24. PMID 1700969.

External links

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