Difference between revisions of "Uterine cervix"

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The '''cervix''', or uterine cervix to be more precise, is the gateway to the uterine corpus.  It is not infrequently afflicited by cancer -- squamous cell carcinoma. Prior to routinue pap tests it was a leading cause of cancer death in women in the Western world.
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 disussed the ''[[cervical polyp]]'' article.
Polyps associated with the cervix are discussed the ''[[cervical polyp]]'' article.


==Introduction==
==Introduction==
Line 9: Line 9:


==Common benign==
==Common benign==
Nabothian cyst:
===Nabothian cyst===
*Simple endocervical cyst.
*Simple endocervical cyst.
**Lined by endocervical epithelial cells.
**Lined by endocervical epithelial cells.
***Columnar morphology with large clear, apical vacuoles.  
***Columnar morphology with large clear, apical vacuoles.  


Tunnel cluster:
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)].
 
===Tunnel cluster===
*Benign proliferation of endocervical glands<ref>[http://pathologyoutlines.com/cervix.html#tunnelclusters http://pathologyoutlines.com/cervix.html#tunnelclusters]</ref>
*Benign proliferation of endocervical glands<ref>[http://pathologyoutlines.com/cervix.html#tunnelclusters http://pathologyoutlines.com/cervix.html#tunnelclusters]</ref>
*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==
==Where to start==
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*CIN I = cytoplasmic halos (koilocytic atypia), atypical cells close to basement membrane only.
*CIN I = cytoplasmic halos (koilocytic atypia), atypical cells close to basement membrane only.
**3:1 enlargement of nucleus vs. normal<ref>[need ref]</ref>
**3:1 enlargement of nucleus vs. normal<ref>[need ref]</ref>
**Binucleation may be seen (ctyopathic effect of HPV)<ref>[need ref]</ref>
**Binucleation may be seen (cytopathic effect of HPV)<ref>[need ref]</ref>
*CIN II = increased nuclear-cytoplasmic ratio, loss of polarity, incr. mitoses, hyperchromasia.
*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.
**If there are large nuclei... you should seen 'em on low power, i.e. 25x.
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Notes:
Notes:
*Hyperchromasia is a very useful feature for identifying CIN (particularily at low power, i.e. 25x).
*Hyperchromasia is a very useful feature for identifying CIN (particularly at low power, i.e. 25x).
*Kiolocytes are the key feature of CIN I.
*Kiolocytes are the key feature of CIN I.
*Kiolocytes are ''not'' considered to be part of a CIN II lesion or CIN III lesion.
*Kiolocytes are ''not'' considered to be part of a CIN II lesion or CIN III lesion.
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Pitfalls:
Pitfalls:
* Squamous metaplasia  
* Squamous metaplasia.
** If you can trace the squamous cells from a gland to the surface it is less likely to be invasive cancer
** 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 http://www.nature.com/modpathol/journal/v15/n3/pdf/3880520a.pdf]
See: [http://www.nature.com/modpathol/journal/v15/n3/pdf/3880520a.pdf http://www.nature.com/modpathol/journal/v15/n3/pdf/3880520a.pdf]


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* Intercellular bridges are often seen/edema is often seen.
* Intercellular bridges are often seen/edema is often seen.
* Uniform cell spacing, i.e. NO crowding.  
* Uniform cell spacing, i.e. NO crowding.  
* NEGATIVES
* NEGATIVES:
** No mitoses (think cancer/CIN if you see 'em)
** No mitoses (think cancer/CIN if you see 'em)
** Usually no hyperchromatism (think cancer/CIN if you see it)
** Usually no hyperchromatism (think cancer/CIN if you see it)
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===IHC===
===IHC===
Uterus vs. cervix<ref>LAE 15 Jan 2009.</ref>
Uterus vs. cervix:<ref>LAE 15 Jan 2009.</ref>
*Cervix (typically): CEA+, p16+
*Cervix (typically): CEA+, p16+.
** ... and ER-, PR-, vimentin-
** ... and ER-, PR-, vimentin-.
*Uterus (typically): vimentin+, ER+, PR+
*Uterus (typically): vimentin+, ER+, PR+.
** ... and CEA-, p16-
** ... and CEA-, p16-.


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


==References==
==References==

Revision as of 19:16, 12 May 2010

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.

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.

Common benign

Nabothian cyst

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

Image:

Tunnel cluster

  • Benign proliferation of endocervical glands[2]
  • Important only as one could mistake minimal deviation adenocarcinoma for it. (???)

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.

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)

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.
    • 3:1 enlargement of nucleus vs. normal[3]
    • Binucleation may be seen (cytopathic effect of HPV)[4]
  • 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.:[5]

Notes:

  • Hyperchromasia is a very useful feature for identifying CIN (particularly at low power, i.e. 25x).
  • Kiolocytes are the key feature of CIN I.
  • Kiolocytes 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.[6]
    • Nucleoli are common in reactive changes.[7]

Kiolocytes versus benign squamous

Kiolocytes:

  • 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. [8]
    • 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.

Cervix cancer grading

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

Ref.:[9]

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[10]

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.

AIS

  • Diagnosis of AIS dependent primarily on nuclear changes:[11]
    • Nuclear crowding.
    • Nuclear hyperchromasia.
    • Cigar-shaped nuclei.
    • +/-Mitoses.
  • Cytoplasm.
    • Hyperchromasia.

Invasive

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.

IHC

Uterus vs. cervix:[12]

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

See also

References

  1. ↑ URL: http://www.med-ed.virginia.edu/Courses/path/gyn/cervix1.cfm. Accessed on: 12 May 2010.
  2. ↑ http://pathologyoutlines.com/cervix.html#tunnelclusters
  3. ↑ [need ref]
  4. ↑ [need ref]
  5. ↑ PBoD P.1075-6.
  6. ↑ STC. Jan 2009.
  7. ↑ STC. Jan 2009.
  8. ↑ V. Dube 2008.
  9. ↑ PBoD P.1077.
  10. ↑ NEED REF.
  11. ↑ need ref
  12. ↑ LAE 15 Jan 2009.
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