Difference between revisions of "Uterine cervix"

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=Introduction=
=Introduction=
*Most cervix cancer is squamous cell carcinoma.
==Overview==
*Most cervix cancer is [[squamous cell carcinoma of the uterine cervix|squamous cell carcinoma]].
**An effective screening test to detect this is the ''Pap test'', which is dealt with in the ''[[gynecologic cytopathology]]'' article.
**An effective screening test to detect this is the ''Pap test'', which is dealt with in the ''[[gynecologic cytopathology]]'' article.
*The work-up of an abnormal ''Pap test'' is a ''colposcopic examination'' and biopsies, which are the topic of ''this'' article.  
*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):<ref name=pmid16148248>{{Cite journal  | last1 = Dresang | first1 = LT. | title = Colposcopy: an evidence-based update. | journal = J Am Board Fam Pract | volume = 18 | issue = 5 | pages = 383-92 | month =  | year =  | doi =  | PMID = 16148248 |URL = www.jabfm.org/cgi/pmidlookup?view=long&pmid=16148248 }}</ref>
*[[High-grade squamous intraepithelial lesion]] ([[HSIL]]).
*Repeated [[low-grade squamous intraepithelial lesion]] ([[LSIL]]).
*[[Atypical squamous cells of undetermined significance]] ([[ASCUS]]) and a positive [[HPV]] test.
*[[ASC-H]].
*[[Atypical glandular cells]] ([[AGC]]) not otherwise specified.
*[[Adenocarcinoma in situ]] ([[AIS]]).
 
==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 intraepithelial neoplasia|Neoplastic cervical lesions]] are typically white.<ref name=pmid23224202>{{Cite journal  | last1 = Zonios | first1 = G. | title = Reflectance model for acetowhite epithelium. | journal = J Biomed Opt | volume = 17 | issue = 8 | pages = 87003-1 | month = Aug | year = 2012 | doi = 10.1117/1.JBO.17.8.087003 | PMID = 23224202 }}</ref>
**[[Squamous metaplasia of the uterine cervix|Squamous metaplasia]] is also white.<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>
*Cervical ectropian (AKA cervical eversion, AKA ectropian) = endocervical epithelium at external os, considered benign, grossly has a granulation tissue-like appearance.<ref name=pmid21270291>{{Cite journal  | last1 = Casey | first1 = PM. | last2 = Long | first2 = ME. | last3 = Marnach | first3 = ML. | title = Abnormal cervical appearance: what to do, when to worry? | journal = Mayo Clin Proc | volume = 86 | issue = 2 | pages = 147-50; quiz 151 | month = Feb | year = 2011 | doi = 10.4065/mcp.2010.0512 | PMID = 21270291 | PMC = 3031439 }}</ref>


==Cervical specimens==
==Cervical specimens==
===Cytology===
* Pap test - see ''[[gynecologic cytopathology]]''.
===Biopsies===
The types of biopsies that are done are:
The types of biopsies that are done are:
# Cervical biopsies - to work-up squamous dysplasia, e.g. [[squamous cell carcinoma of the uterine cervix]].
# Cervical biopsies - prompted by abnormal Pap test, e.g. [[HSIL]], to look for [[squamous cell carcinoma of the uterine cervix]].
# Endocervical curettage (ECC) - to work-up columnar dysplasia, e.g. [[endocervical adenocarcinoma]]/[[endometrial adenocarcinoma]].
# Endocervical curettage (ECC) - to work-up columnar dysplasia, e.g. [[endocervical adenocarcinoma]]/[[endometrial adenocarcinoma]].
# Endometrial curettage (endometrial biopsy) - covered in the ''[[endometrium]]'' article.
 
===Surgical specimens===
# [[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 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>
 
===Other===
*Total abdominal hysterectomy - for non-cervical pathology, e.g. [[uterine leiomyoma]]s, [[uterine adenomyosis]].
*Radical hysterectomy - for [[endometrial carcinoma]] with endocervical involvement.


=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==
===Microscopic===
Features:
*Small round cells.
*Usually no halos.
**May be seen in pseudokoilocytes.
*No nuclear membrane irregularities.
*No nuclear hyperchromasia.
===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/2796932803/in/photostream/ CIN I versus normal (flickr.com/euthman)].
===Sign out===
<pre>
UTERINE CERVIX, BIOPSY:
- TRANSFORMATION ZONE WITHOUT APPARENT PATHOLOGY.
- NEGATIVE FOR DYSPLASIA.
</pre>
<pre>
UTERINE CERVIX, BIOPSY:
- SQUAMOUS MUCOSA WITHOUT APPARENT PATHOLOGY.
- STRIPPED ENDOCERVICAL EPITHELIUM WITHOUT APPARENT PATHOLOGY.
- NEGATIVE FOR DYSPLASIA.
</pre>


==Endocervical glands==
==Endocervical glands==
===Microscopic===
Features:
Cervical glands normally have round nuclei and vaguely resemble the colonic mucosa.   
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.
*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===
<pre>
UTERINE ENDOCERVIX, CURETTAGE:
- ENDOCERVICAL MUCOSA AND STRIPPED ENDOCERVICAL EPITHELIUM WITHIN NORMAL LIMITS.
</pre>


Memory device: The Cs (Cervix & Colon) are similar.
====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>


==Sign out==
====Squamous epithelium present====
<pre>
<pre>
UTERINE ENDOCERVIX, CURETTAGE:  
UTERINE ENDOCERVIX, CURETTAGE:  
- ENDOCERVICAL MUCOSA WITHIN NORMAL LIMITS.  
- ENDOCERVICAL MUCOSA WITHIN NORMAL LIMITS.  
- SCANT NON-PROLIFERATIVE ENDOMETRIUM.
- SQUAMOUS EPITHELIUM WITHOUT APPARENT PATHOLOGY.
</pre>
 
====Endometrium present====
<pre>
UTERINE ENDOCERVIX, CURETTAGE:
- ENDOCERVICAL MUCOSA WITHIN NORMAL LIMITS.
- SCANT NON-PROLIFERATIVE ENDOMETRIUM.
</pre>
 
====Inflamed====
<pre>
UTERINE ENDOCERVIX, CURETTAGE:
- INFLAMED ENDOCERVICAL MUCOSA.
- REACTIVE SQUAMOUS EPITHELIUM.
- NEGATIVE FOR MALIGNANCY.
</pre>
 
<pre>
UTERINE ENDOCERVIX, CURETTAGE:
- BENIGN INFLAMED ENDOCERVICAL MUCOSA.
- STRIPPED ENDOCERVICAL EPITHELIUM WITHIN NORMAL LIMITS.
</pre>
 
====No stroma present====
<pre>
UTERINE ENDOCERVIX, CURETTAGE:
- STRIPPED ENDOCERVICAL EPITHELIUM WITHOUT APPARENT PATHOLOGY.
</pre>
 
====Limited tissue====
<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>
 
<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. Clinical correlation is
suggested.
</pre>
 
<pre>
UTERINE ENDOCERVIX, CURETTAGE:
- BENIGN SQUAMOUS EPITHELIUM WITH METAPLASTIC CHANGE.
- 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>


Line 39: Line 202:
==Endocervix==
==Endocervix==
===Sign out===
===Sign out===
====No stroma====
====No endocervical epithelium====
<pre>
<pre>
UTERINE ENDOCERVIX, CURETTAGE:  
UTERINE ENDOCERVIX, CURETTAGE:  
- STRIPPED ENDOCERVICAL EPITHELIUM WITHOUT APPARENT PATHOLOGY.  
- SQUAMOUS EPITHELIUM WITHOUT APPARENT PATHOLOGY.
- ASSESSMENT LIMITED AS NO DEFINITE ENDOCERVICAL STROMA IS PRESENT.
- NO ENDOCERVICAL EPITHELIUM IDENTIFIED.
- MUCOUS AND INFLAMMATORY CELLS.
</pre>
 
====No epithelium====
<pre>
UTERINE ENDOCERVIX, CURETTAGE:
- MUCOUS AND INFLAMMATORY CELLS.
- NO EPITHELIUM IDENTIFIED.
</pre>
</pre>


Line 49: Line 220:
<pre>
<pre>
UTERINE ENDOCERVIX, CURETTAGE:  
UTERINE ENDOCERVIX, CURETTAGE:  
- NO TISSUE PRESENT, SEE COMMENT.  
- NO TISSUE PRESENT, SEE COMMENT.  


COMMENT:  
COMMENT:  
No tissue identified on gross or microscopy.
No tissue identified on gross or microscopy.
</pre>
<pre>
UTERINE ENDOCERVIX, CURETTAGE:
- NO TISSUE PRESENT, SEE COMMENT.
COMMENT:
No tissue identified on microscopy. No tissue is seen on inspection of the paraffin block.
</pre>
</pre>


Line 61: Line 240:
#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===
*Benign.
*Common.
===Gross===
*Bump.
*Pale colour.
DDx - clinical:
*[[Benign endocervical polyp]].
====Image====
<gallery>
Image:Ovula_nabothi.jpg | Nabothian cyst. (WC/euthman)
</gallery>
===Microscopic===
Features:
Features:
*Simple endocervical cyst.
*Simple endocervical cyst.
**Lined by endocervical epithelial cells.
**Usually lined by endocervical epithelial cells - may be flattened.
***Columnar morphology with large clear, apical vacuoles.  
***Columnar morphology with large clear, apical vacuoles.  
**+/-Macrophages.
**+/-Mucus.
Note:
*May be lined by tubal epithelium.
**Cilia.
**High [[NC ratio]] ~ 1:1.{{fact}}


Image:
Image:
*[http://www.gfmer.ch/selected_images_v2/detail_list.php?cat1=4&cat2=23&cat3=130&cat4=5&stype=n Nabothian cyst (gfmer.ch)].
*[http://www.gfmer.ch/selected_images_v2/detail_list.php?cat1=4&cat2=23&cat3=130&cat4=5&stype=n Nabothian cyst (gfmer.ch)].
===Sign out===
<pre>
CERVICAL POLYP, REMOVAL:
- BENIGN POLYPOID FRAGMENT OF EXOCERVICAL MUCOSA WITH NABOTHIAN CYSTS AND
BENIGN ENDOCERVICAL EPITHELIUM.
</pre>
<pre>
POLYPOID LESION ("CERVICAL POLYP"), EXCISION:
- POLYPOID NABOTHIAN CYST.
</pre>


==Tunnel cluster==
==Tunnel cluster==
Line 75: Line 299:
*Benign.<ref name=pmid12352183>{{Cite journal  | last1 = Nucci | first1 = MR. | title = Symposium part III: tumor-like glandular lesions of the uterine cervix. | journal = Int J Gynecol Pathol | volume = 21 | issue = 4 | pages = 347-59 | month = Oct | year = 2002 | doi =  | PMID = 12352183 }}</ref>
*Benign.<ref name=pmid12352183>{{Cite journal  | last1 = Nucci | first1 = MR. | title = Symposium part III: tumor-like glandular lesions of the uterine cervix. | journal = Int J Gynecol Pathol | volume = 21 | issue = 4 | pages = 347-59 | month = Oct | year = 2002 | doi =  | PMID = 12352183 }}</ref>
*Not the same as ''[[microglandular hyperplasia]]''.<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>
*Not the same as ''[[microglandular hyperplasia]]''.<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>
*Considered a special type of [[nabothian cyst]].<ref name=pmid12640157>{{Cite journal  | last1 = Okamoto | first1 = Y. | last2 = Tanaka | first2 = YO. | last3 = Nishida | first3 = M. | last4 = Tsunoda | first4 = H. | last5 = Yoshikawa | first5 = H. | last6 = Itai | first6 = Y. | title = MR imaging of the uterine cervix: imaging-pathologic correlation. | journal = Radiographics | volume = 23 | issue = 2 | pages = 425-45; quiz 534-5 | month =  | year =  | doi =  | PMID = 12640157 | URL = http://radiographics.rsna.info/content/23/2/425.full }}</ref>


===Microscopic===
===Microscopic===
Line 89: Line 314:
#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==
:'''''Not''' to be confused with [[microglandular adenosis]]''.
:'''''Not''' to be confused with [[microglandular adenosis]]''.
*Abbreviated ''MGH''.
*Abbreviated ''MGH''.
===General===
*[[AKA]] ''microglandular change''.
*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>
{{Main|Microglandular hyperplasia}}
 
===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:
*[[Adenocarcinoma of the uterine cervix]], in situ.
*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>
 
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.


==Wolffian duct hyperplasia==
==Wolffian duct hyperplasia==
Line 141: Line 340:
*Abundant small tubules with a simple cuboidal epithelium.
*Abundant small tubules with a simple cuboidal epithelium.
*Round small bland nucleus.
*Round small bland nucleus.
DDx:
*[[Wolffian duct remnant]].


===Stains===
===Stains===
Line 146: Line 348:


==Squamous metaplasia of the uterine cervix==
==Squamous metaplasia of the uterine cervix==
*Abbreviated ''SMC''.
{{Main|Squamous metaplasia of the uterine cervix}}
==Reactive squamous epithelium of the uterine cervix==
*[[AKA]] ''reactive squamous epithelium''.
*[[AKA]] ''reactive changes''.
===General===
===General===
*Benign process: columnar cells -> squamoid cells.
*Common.
**Biologic response to irritation and/or inflammation.
*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===
Features:
Features:
* Nuclei are uniform size and round.
#Inflammation - '''key feature'''.
** [[Nucleoli]] present.
#*Lymphocytes.
* +/-Intercellular bridges (due to edema) - common.
#*Plasma cells.
* Uniform cell spacing, i.e. no crowding.  
#Mild nuclear enlargement. †
#Nucleoli - '''important'''.


Negatives:
Note:
* No mitoses (think cancer/CIN if you see 'em).
*† Normal squamous cell nuclei are approximately 8 μm.<ref>URL: [http://www.curran.pwp.blueyonder.co.uk/cytology.htm http://www.curran.pwp.blueyonder.co.uk/cytology.htm]. Accessed on: 5 November 2012.</ref>
* Usually no hyperchromatism (think cancer/CIN if you see it).
**Mild enlargement ~ 2-3x normal.
 
**CIN I nuclei are ~ 3x normal (24 μm).
Notes:
*NC ratio high - possible to confuse CIN III.


DDx:
DDx:
*[[CIN III]].
*[[Cervical intraepithelial neoplasia I]].
*[[Squamous cell carcinoma of the uterine cervix]].
*[[CIN II|Cervical intraepithelial neoplasia II]].
*[[NILM]].


===IHC===
===IHC===
*p16 +ve - in SCC; a poor man's test for [[HPV]].
*p16 -ve.
*Ki-67 - stains a large number of cells; proliferation marker.


=Non-invasive=
===Sign out===
==Cervical intraepithelial neoplasia==
<pre>
:''CIN I'', ''CIN II'' and ''CIN III'' redirect to here.
UTERINE CERVIX, BIOPSY:
*Abbreviated ''CIN''.
- REACTIVE SQUAMOUS EPITHELIUM.
- BENIGN ENDOCERVICAL GLANDS.
- NEGATIVE FOR MALIGNANCY.
</pre>
 
<pre>
COMMENT:
The squamous epithelium is negative for p16 staining. Ki-67 staining is predominantly in
the lower third of the epithelium.
</pre>


==Tubal metaplasia of the uterine cervix==
*[[AKA]] ''tubal metaplasia'', abbreviated ''TM''.
===General===
===General===
*Refers to changes in squamous epithelium.
*Benign.
*Mimics the appearance of [[Endocervical adenocarcinoma in situ|AIS]] - especially at low power.


Grades (squamous intraepithelial neoplasia):
===Microscopic===
*CIN I = mild dysplasia.
Features - like the [[fallopian tube]]:
*CIN II = moderate dysplasia.
*Nuclear crowding vis-à-vis benign endocervical epithelium (low power).
*CIN III = severe dysplasia.
*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.


Bethesda system:
DDx:
*LSIL ([[low-grade squamous intraepithelial lesion]]) = CIN I.
*[[Endocervical adenocarcinoma in situ]].
*HSIL ([[high-grade squamous intraepithelial lesion]]) = CIN II, CIN III.


====Treatment====
Image:
*[[LSIL]]: nothing, as usually regress.
*[http://www.nature.com/modpathol/journal/v13/n3/fig_tab/3880047f17.html Tubal metaplasia (nature.com)].
*[[HSIL]]: excision (e.g. cone, [[LEEP]], laser) + follow-up.


[[Loop electrosurgical excision procedure]] (LEEP):
===IHC===
*Used for squamous lesions -- pathologist typically gets several pieces.
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.
*CEA -ve/+ve.
*p16 -ve.{{fact}}
 
==Atrophy of the uterine cervix==
*[[AKA]] ''cervical atrophy''.
*[[AKA]] ''atrophy of the cervix''.
*[[AKA]] ''cervix with atrophic changes''.
{{Main|Uterine cervix with atrophic changes}}


Cone:
==Radiation changes of the endocervical epithelium==
*Used for endocervical lesions, i.e. adenocarcinoma in situ (AIS).
{{Main|Radiation changes}}
*Pathologist gets a ring or donut-shaped piece of tissue.
{{Main|Radiation changes in cervical cytology}}
===General===
*Uncommon.
*Clinical history: radiation treatment for cervical carcinoma.<ref name=pmid2209348/>


===Microscopic===
===Microscopic===
====CIN I====
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>
Features - CIN I:<ref name=Ref_PBoD1075-6>{{Ref PBoD|1075-6}}</ref>
*Nuclear enlargement with a normal [[NC ratio]].
*"Koilocytic atypia":<ref name=Ref_GP146>{{Ref GP|146}}</ref>
*+/-Coarse chromatin.
**Cytoplasmic halos.
*+/-Nucleoli.
**Nuclear enlargement >=3:1 enlarged nucleus:normal nucleus.
*+/-Multinucleation - very common.
**Nuclear membrane irregularities.
*Histiocytes - common.
**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:
==Reactive endocervical cells==
*Atypical cells usually close to basement membrane.
===General===
**May be seen, focally, in the upper layers.<ref name=Ref_GP146>{{Ref GP|146}}</ref>
*Benign.


====CIN II====
===Microscopic===
Features - CIN II:<ref name=Ref_PBoD1075-6>{{Ref PBoD|1075-6}}</ref>
Features:
*Increased nuclear-cytoplasmic ratio, loss of polarity, incr. mitoses, hyperchromasia.
*Mild nuclear enlargement.
**If there are large nuclei... you should seen 'em on low power, i.e. 25x.
*+/-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>
 
====CIN 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>


====Koilocytes versus benign squamous====
====Images====
Koilocytes:
<gallery>
*Perinuclear clearing.
Image: Endocervical epithelium with multinucleation -- high mag.jpg | Multinucleated endocervix - high mag.
*Nuclear changes.  
Image: Endocervical epithelium with multinucleation -- very high mag.jpg | Multinucleated endocervix - very high mag.
**Size similar (or larger) to those in the basal layer of the epithelium.
Image: Endocervical epithelium with multinucleation -- extremely high mag.jpg | Multinucleated endocervix - extremely high mag.
**Nuclear enlargement should be evident on low power, i.e. 25x. <ref>V. Dube 2008.</ref>
</gallery>
**Central location - nucleus should be smack in the middle of the cell.
www:
*[http://www.surgpath4u.com/caseviewer.php?case_no=229 Reactive endocervical cells (surgpath4u.com)].


Notes:
=Non-invasive=
# Both perinuclear clearing and nuclear changes are essential.
==Cervical intraepithelial neoplasia==
# Benign cells have a small nucleus that is peripheral.
*Previously known as ''cervical intraepithelial neoplasia'' and ''cervical dysplasia''.
 
{{Main|Squamous intraepithelial lesion of the uterine cervix}}
===IHC===
*p16 +ve.
*Ki-67 +ve above basal layer.
 
Images:
*[http://www.mtmlabs.com/us/index.php?view=article&catid=3%3Aprodukte&id=107%3Acintecr-p16ink4a-staining-atlas&tmpl=component&print=1&layout=default&page=&option=com_content&Itemid=11 Altas of p16 staining (mtmlabs.com)].
 
===Sign-out===
<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, BIOPSY:
- CERVICAL INTRAEPITHELIAL NEOPLASIA 3 (SEVERE DYSPLASIA).
</pre>


==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).
 
===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.
#*Normal gland depth (subjective).
 
DDx:
*[[Endocervical adenocarcinoma]].
*[[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.


=Cancer=
=Cancer=
Line 304: 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:
*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.
 
Grading:<ref>{{Ref PBoD|1077}}</ref>
#Well-differentiated (keratinizing).
#Moderately differentiated (nonkeratinizing).
#Poorly differentiated.
 
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]].


==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.
 
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===
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=
There are a number of uncommon type of cervical cancer.
There are a number of uncommon type of cervical cancer.


==Adenosquamous carcinoma==
==Serous carcinoma of the uterine cervix==
Features:
*Morphologic features of both squamous carcinoma and adenocarcinoma:
**Adenocarcinoma: gland forming ''or'' mucin vacuoles.
**[[Squamous carcinoma]]: abundant eosinophilic cytoplasm, central nucleus.
 
Image: [http://commons.wikimedia.org/wiki/File:Adenosquamous_carcinoma_high_mag.jpg Adenosquamous carcinoma - high mag. (WC)].
 
==Clear cell carcinoma of the uterine cervix==
*[[AKA]] ''cervical clear cell carcinoma''.
===General===
===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>
*Poor prognosis.<ref name=pmid21876330>{{Cite journal  | last1 = Togami | first1 = S. | last2 = Kasamatsu | first2 = T. | last3 = Sasajima | first3 = Y. | last4 = Onda | first4 = T. | last5 = Ishikawa | first5 = M. | last6 = Ikeda | first6 = S. | last7 = Kato | first7 = T. | last8 = Tsuda | first8 = H. | title = Serous adenocarcinoma of the uterine cervix: a clinicopathological study of 12 cases and a review of the literature. | journal = Gynecol Obstet Invest | volume = 73 | issue = 1 | pages = 26-31 | month =  | year = 2012 | doi = 10.1159/000329319 | PMID = 21876330 }}</ref>
*Less common in the cervix - when compared to other gynecologic sites.<ref name=Ref_WMSP442>{{Ref WMSP|442}}</ref>
*Extremely rare.
**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>
===Microscopic===
===Microscopic===
Features:
Features:
*Like [[clear cell carcinoma]] elsewhere:
*Like other [[serous carcinoma]]s.
**+/-Clear cytoplasm.
**Cells have large free/luminal surface area (hobnailing pattern) and small non-free surface.
**Moderate-to-severe [[nuclear pleomorphism]].


DDx:
==Adenosquamous carcinoma of the uterine cervix==
*[[Clear cell carcinoma of the endometrium]].
{{Main|Adenosquamous carcinoma of the uterine cervix}}
*[[Serous carcinoma of the endometrium]].
 
*Serous carcinoma of the cervix.
==Clear cell carcinoma of the uterine cervix==
{{Main|Clear cell carcinoma of the uterine cervix}}


==Small cell carcinoma of the cervix==
==Small cell carcinoma of the cervix==
Line 455: Line 529:
*Nests of cells with basaloid rim and squamoid center.
*Nests of cells with basaloid rim and squamoid center.
**Basaloid cells look benign.
**Basaloid cells look benign.
DDx:
*Ectopic [[prostate gland]].


Image:
Image:
Line 460: 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>
 
===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:
*[[Squamous carcinoma]].
 
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 507: 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==
==Mucoepidermoid carcinoma of the uterine cervix==
{{Main|Mucoepidermoid carcinoma}}
{{Main|Mucoepidermoid carcinoma}}
===General===
===General===
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===Microscopic===
===Microscopic===
Features:<ref name=pmid19092631/>
Features:<ref name=pmid1700969/>
*Like [[salivary gland]] tumour.
*[[Squamous cell carcinoma]]-like with:
*#No glands formation.
*#Intracellular mucin.
*#*Classically have ''mucous cells'' - cells with abundant fluffy cytoplasm and large mucin vacuoles - '''key feature'''.
 
Notes:
*Similar to the [[salivary gland]] tumour.<ref name=pmid19092631/>
 
DDx:
*[[Cervical intraepithelial neoplasia]], i.e. [[CIN II]], [[CIN III]].
*Adenosquamous carcinoma.
 
===Stains===
Mucin stains:<ref name=pmid1700969/>
*[[Alcian blue stain]] 
*[[PAS-D|Periodic acid-Schiff-diastase stain]].
 
===IHC===
*CEA +ve.<ref name=pmid1700969>{{Cite journal  | last1 = Thelmo | first1 = WL. | last2 = Nicastri | first2 = AD. | last3 = Fruchter | first3 = R. | last4 = Spring | first4 = H. | last5 = DiMaio | first5 = T. | last6 = Boyce | first6 = J. | title = Mucoepidermoid carcinoma of uterine cervix stage IB. Long-term follow-up, histochemical and immunohistochemical study. | journal = Int J Gynecol Pathol | volume = 9 | issue = 4 | pages = 316-24 | month =  | year = 1990 | doi =  | PMID = 1700969 }}</ref>


===Molecular===
===Molecular===
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==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/>


=See also=
=See also=
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*[[Cervical polyp]].
*[[Cervical polyp]].
*[[Gynecologic cytopathology]].
*[[Gynecologic cytopathology]].
*[[Gynecologic pathology]].


=References=
=References=
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=External links=
=External links=
*[http://www.mtmlabs.com/us/index.php?option=com_content&view=article&id=107&Itemid=11 Interpretation altas for p16 staining (mtmlabs.com)].
*[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
48,466

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