Difference between revisions of "Uterine cervix"

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(fix sp. of koilocyte)
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[[Cytopathology]] of the cervix is dealt with in the ''[[gynecologic cytopathology]]'' article.
[[Cytopathology]] of the cervix is dealt with in the ''[[gynecologic cytopathology]]'' article.


==Introduction==
=Introduction=
*Consists of non-keratinized squamous epithelium and simple columnar epithelium.   
*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>
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*Most cervix cancer is squamous cell carcinoma.
*Most cervix cancer is squamous cell carcinoma.


==Common benign==
=Normal histology=
===Nabothian cyst===
==Endocervical glands==
Cervical glands normally have round nuclei and vaguely resemble the colonic mucosa. 
*If the nuclei are columnar think cancer!  This is like in the colon-- columnar nuclei = badness.
 
Memory device: The Cs (Cervix & Colon) are similar.
 
=Where to start=
#Identify epithelium - exocervical (stratified squamous), endocervical (simple columnar), both.
#*If there is both exocervix and endocervix --> transition zone.
#Identify possible squamous lesions.
#Identify possible endocervical lesions.
 
=Benign (common)=
==Nabothian cyst==
Features:
*Simple endocervical cyst.
*Simple endocervical cyst.
**Lined by endocervical epithelial cells.
**Lined by endocervical epithelial cells.
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*[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)].


===Tunnel cluster===
==Tunnel cluster==
*Benign proliferation of endocervical glands<ref>[http://pathologyoutlines.com/cervix.html#tunnelclusters http://pathologyoutlines.com/cervix.html#tunnelclusters]</ref>
Features:
*Benign proliferation of endocervical glands.<ref>URL: [http://pathologyoutlines.com/cervix.html#tunnelclusters http://pathologyoutlines.com/cervix.html#tunnelclusters]. Accessed on: 27 February 2011.</ref>
 
Notes:
*Important only as one could mistake minimal deviation adenocarcinoma for it. (???)
*Important only as one could mistake minimal deviation adenocarcinoma for it. (???)


==Where to start==
=Non-invasive=
#Identify epithelium - exocervical (stratified squamous), endocervical (simple columnar), both.
#*If there is both exocervix and endocervix --> transition zone.
#Identify possible squamous lesions.
#Identify possible endocervical lesions.
 
==Endocervical glands==
Cervical glands normally have round nuclei and vaguely resemble the colonic mucosa. 
*If the nuclei are columnar think cancer!  This is like in the colon-- columnar nuclei = badness.
 
Mnemonic: The Cs (Cervix & Colon) are similar.
 
==Cervical intraepithelial neoplasia (CIN)==
==Cervical intraepithelial neoplasia (CIN)==
Refers to changes in squamous epithelium.
Refers to changes in squamous epithelium.
Line 93: Line 99:
# Benign cells have a small nucleus that is peripheral.
# Benign cells have a small nucleus that is peripheral.


=Cancer=
==Cervix cancer grading==
==Cervix cancer grading==
#Well-differentiated (keratinizing).
#Well-differentiated (keratinizing).
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#Poorly differentiated.
#Poorly differentiated.
Ref.:<ref>{{Ref PBoD|1077}}</ref>
Ref.:<ref>{{Ref PBoD|1077}}</ref>
==Squamous cell carcinoma (SCC)==
{{Main|Squamous cell carcinoma}}
The most common type of cervical cancer.


===SCC of the cervix versus CIN III===
===SCC of the cervix versus CIN III===
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** ... and CEA-, p16-.
** ... and CEA-, p16-.


==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===
==Adenosquamous carcinoma==
A mixed of morphologic features seen in squamous carcinoma and adenocarcinoma.
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 (WC)].
Image: [http://commons.wikimedia.org/wiki/File:Adenosquamous_carcinoma_high_mag.jpg Adenosquamous carcinoma - high mag. (WC)].


===Clear cell carcinoma===
==Clear cell carcinoma==
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>
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>


===Adenoid basal carcinoma===
==Adenoid basal carcinoma==
===General===
*Good prognosis.<ref name=pmid9438010>{{cite journal |author=Senzaki H, Osaki T, Uemura Y, ''et al.'' |title=Adenoid basal carcinoma of the uterine cervix: immunohistochemical study and literature review |journal=Jpn. J. Clin. Oncol. |volume=27 |issue=6 |pages=437–41 |year=1997 |month=December |pmid=9438010 |doi= |url=http://jjco.oxfordjournals.org/cgi/content/full/27/6/437}}</ref>
*Good prognosis.<ref name=pmid9438010>{{cite journal |author=Senzaki H, Osaki T, Uemura Y, ''et al.'' |title=Adenoid basal carcinoma of the uterine cervix: immunohistochemical study and literature review |journal=Jpn. J. Clin. Oncol. |volume=27 |issue=6 |pages=437–41 |year=1997 |month=December |pmid=9438010 |doi= |url=http://jjco.oxfordjournals.org/cgi/content/full/27/6/437}}</ref>


===Microscopic===
Features:<ref name=pmid9438010>{{cite journal |author=Senzaki H, Osaki T, Uemura Y, ''et al.'' |title=Adenoid basal carcinoma of the uterine cervix: immunohistochemical study and literature review |journal=Jpn. J. Clin. Oncol. |volume=27 |issue=6 |pages=437–41 |year=1997 |month=December |pmid=9438010 |doi= |url=http://jjco.oxfordjournals.org/cgi/content/full/27/6/437}}</ref>
Features:<ref name=pmid9438010>{{cite journal |author=Senzaki H, Osaki T, Uemura Y, ''et al.'' |title=Adenoid basal carcinoma of the uterine cervix: immunohistochemical study and literature review |journal=Jpn. J. Clin. Oncol. |volume=27 |issue=6 |pages=437–41 |year=1997 |month=December |pmid=9438010 |doi= |url=http://jjco.oxfordjournals.org/cgi/content/full/27/6/437}}</ref>
*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.


==See also==
=See also=
*[[Vulvar intraepithelial neoplasia]].
*[[Vulvar intraepithelial neoplasia]].
*[[Cervical polyp]].
*[[Cervical polyp]].
*[[Gynecologic cytopathology]].
*[[Gynecologic cytopathology]].


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


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

Revision as of 02:40, 28 February 2011

The cervix, or uterine cervix to be more precise, 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 cervix is dealt with in the gynecologic cytopathology article.

Introduction

  • Consists of non-keratinized squamous epithelium and simple columnar epithelium.
  • The area of overlap (between squamous & columnar) is known as the "transformation zone".[1]
    • Also known as "transition zone".
  • Most cervix cancer is squamous cell carcinoma.

Normal histology

Endocervical glands

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

  • If the nuclei are columnar think cancer! This is like in the colon-- columnar nuclei = badness.

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

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 (common)

Nabothian cyst

Features:

  • Simple endocervical cyst.
    • Lined by endocervical epithelial cells.
      • Columnar morphology with large clear, apical vacuoles.

Image:

Tunnel cluster

Features:

  • Benign proliferation of endocervical glands.[2]

Notes:

  • Important only as one could mistake minimal deviation adenocarcinoma for it. (???)

Non-invasive

Cervical intraepithelial neoplasia (CIN)

Refers to changes in squamous epithelium.

Grades (squamous intraepithelial neoplasia):

  • CIN I = mild dysplasia.
  • CIN II = moderate dysplasia.
  • CIN III = severe dysplasia.

Bethesda system:

  • LSIL (low-grade squamous intraepithelial lesion) = CIN I.
  • HSIL (high-grade squamous intraepithelial lesion) = CIN II, CIN III.

Treatment

  • LSIL: nothing, as usually regress.
  • HSIL: excision (e.g. cone, LEEP, laser) + followup.

LEEP = Loop Electrosurgical Excision Procedure (LEEP) Procedure.

  • Used for squamous lesions -- pathologist typically gets several pieces.

Cone

  • Used for endocervical lesions, i.e. adenocarcinoma in situ (AIS).
  • Pathologist gets a ring or donut-shaped piece of tissue.

Histologic changes in CIN I, CIN II and CIN III

  • CIN I = cytoplasmic halos (koilocytic atypia), atypical cells close to basement membrane only.
    • Nuclear enlargement -- >=3:1 enlarged nucleus:normal nucleus.
    • Binucleation may be seen (cytopathic effect of HPV).[3]
  • CIN II = increased nuclear-cytoplasmic ratio, loss of polarity, incr. mitoses, hyperchromasia.
    • If there are large nuclei... you should seen 'em on low power, i.e. 25x.
  • CIN III = same changes as in CIN II + outer third (or full thickness).

Ref.:[4]

Notes:

  • Hyperchromasia is a very useful feature for identifying CIN (particularly at low power, i.e. 25x).
  • Koilocytes are the key feature of CIN I.
  • Koilocytes are not considered to be part of a CIN II lesion or CIN III lesion.
  • 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) = at least CIN I.
    • If there is a mitosis in the middle third (of the epithelial layer) = at least CIN II.
    • If there is a mitosis in the outer third = CIN III.
  • Nucleoli are usually NOT present in CIN.[5]
    • Nucleoli are common in reactive changes.[6]

Koilocytes versus benign squamous

Koilocytes:

  • Perinuclear clearing.
  • Nuclear changes.
    • Size similar (or larger) to those in the basal layer of the epithelium.
    • Nuclear enlargement should be evident on low power, i.e. 25x. [7]
    • Central location - nucleus should be smack in the middle of the cell.

Notes:

  1. Both perinuclear clearing and nuclear changes are essential.
  2. Benign cells have a small nucleus that is peripheral.

Cancer

Cervix cancer grading

  1. Well-differentiated (keratinizing).
  2. Moderately differentiated (nonkeratinizing).
  3. Poorly differentiated.

Ref.:[8]

Squamous cell carcinoma (SCC)

Main article: Squamous cell carcinoma

The most common type of cervical cancer.

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.

Pitfalls:

  • Squamous metaplasia.
    • If you can trace the squamous cells from a gland to the surface it is less likely to be invasive cancer.

See: http://www.nature.com/modpathol/journal/v15/n3/pdf/3880520a.pdf

Squamous metaplasia

Squamous metaplasia is a response to inflammation...

  • Nuclei are uniform size and round.
  • Intercellular bridges are often seen/edema is often seen.
  • Uniform cell spacing, i.e. NO crowding.
  • NEGATIVES:
    • No mitoses (think cancer/CIN if you see 'em).
    • Usually no hyperchromatism (think cancer/CIN if you see it).

Notes:

  • It is possible to confuse CIN III with squamous metaplasia.

IHC:

  • p16 (poor man's test for HPV).
  • Ki-67 (proliferation marker).

Adenocarcinoma

  • Adenocarcinoma of the cervix/adenocarcinoma in situ (AIS) of the cervis is much less common than squamous dysplasia of the cervix/SCC of the cervix.
  • AIS/adenocarcinoma arises can arise from the endocervical glands.

Adenocarcinoma in situ (AIS)

  • Diagnosis of AIS dependent primarily on nuclear changes:
    • Nuclear crowding.
    • Nuclear hyperchromasia.
    • Cigar-shaped nuclei.
    • +/-Mitoses.
  • Cytoplasm.
    • Hyperchromasia.

Invasive adenocarcinoma

Features:

Notes:

  • AIS changes - similar to 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.

IHC

Uterus vs. cervix:[9]

  • Cervix (typically): CEA+, p16+.
    • ... and ER-, PR-, vimentin-.
  • Uterus (typically): vimentin+, ER+, PR+.
    • ... and CEA-, p16-.

Uncommon types of cervical cancer

There are a number of uncommon type of cervical cancer.

Adenosquamous carcinoma

Features:

  • Morphologic features of both squamous carcinoma and adenocarcinoma:
    • Adenocarcinoma: gland forming or mucin vacuoles.
    • Squamous carcinoma: abundant eosinophilic cytoplasm, central nucleus.

Image: Adenosquamous carcinoma - high mag. (WC).

Clear cell carcinoma

Associated with diethylstilbestrol exposure in utero.[10]

Adenoid basal carcinoma

General

Microscopic

Features:[11]

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

See also

References

  1. ↑ URL: http://www.med-ed.virginia.edu/Courses/path/gyn/cervix1.cfm. Accessed on: 12 May 2010.
  2. ↑ URL: http://pathologyoutlines.com/cervix.html#tunnelclusters. Accessed on: 27 February 2011.
  3. ↑ Roteli-Martins CM, Derchain SF, Martinez EZ, Siqueira SA, Alves VA, Syrjänen KJ (2001). "Morphological diagnosis of HPV lesions and cervical intraepithelial neoplasia (CIN) is highly reproducible". Clin Exp Obstet Gynecol 28 (2): 78–80. PMID 11491378.
  4. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 1075-6. ISBN 0-7216-0187-1.
  5. ↑ STC. January 2009.
  6. ↑ STC. January 2009.
  7. ↑ V. Dube 2008.
  8. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 1077. ISBN 0-7216-0187-1.
  9. ↑ LAE. 15 January 2009.
  10. ↑ van Dijck, JA.; Doorduijn, Y.; Bulten, JH.; Verloop, J.; Massuger, LF.; Kiemeney, BA. (2009). "[Vaginal and cervical cancer due to diethylstilbestrol (DES); end epidemic]". Ned Tijdschr Geneeskd 153: A366. PMID 19857300.
  11. ↑ 11.0 11.1 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.
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