Difference between revisions of "Squamous intraepithelial lesion of the uterine cervix"

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Squamous intraepithelial lesion of the uterine cervix (view source)

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===Treatment===
===Treatment===
Overview:
Overview:
*[[LSIL]]: nothing, as usually regress.   
*[[LSIL]]: follow-up, as it usually regress.   
*[[HSIL]]: excision (e.g. cone, [[LEEP]], laser) + follow-up.
*[[HSIL]]: excision (e.g. [[cervical cone|cone]], [[LEEP]], laser) + follow-up.


====Procedures====  
====Procedures====  
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==Microscopic==
==Microscopic==
===Low-grade squamous intraepithelial lesion===
===Low-grade squamous intraepithelial lesion===
Features - LSIL:<ref name=Ref_PBoD1075-6>{{Ref PBoD|1075-6}}</ref>
{{Main|Low-grade squamous intraepithelial lesion}}
*"Koilocytic atypia":<ref name=Ref_GP146>{{Ref GP|146}}</ref>
**Cytoplasmic halos.
**Nuclear enlargement >=3:1 enlarged nucleus:normal nucleus.
**Nuclear membrane irregularities.
**Nuclear hyperchromasia.
**Coarse chromatin.
**Binucleation may be seen (cytopathic effect of [[HPV]]).<ref name=pmid11491378>{{cite journal |author=Roteli-Martins CM, Derchain SF, Martinez EZ, Siqueira SA, Alves VA, Syrjänen KJ |title=Morphological diagnosis of HPV lesions and cervical intraepithelial neoplasia (CIN) is highly reproducible |journal=Clin Exp Obstet Gynecol |volume=28 |issue=2 |pages=78–80 |year=2001 |pmid=11491378 |doi= |url=}}</ref>
 
Note:
*Atypical cells usually close to basement membrane.
**May be seen, focally, in the upper layers.<ref name=Ref_GP146>{{Ref GP|146}}</ref>
 
====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. <ref>V. Dube 2008.</ref>
**Central location - nucleus should be smack in the middle of the cell.
 
Notes:
# Both perinuclear clearing and nuclear changes are essential.
# Benign cells have a small nucleus that is peripheral.
 
====Images====
<gallery>
Image: Low-grade squamous intraepithelial lesion -- intermed mag.jpg | LSIL - intermed. mag. (WC)
Image: Low-grade squamous intraepithelial lesion -- p16 - intermed mag.jpg | LSIL - intermed. mag. (WC)
Image: Low-grade squamous intraepithelial lesion -- high mag.jpg | LSIL - high mag. (WC)
Image: Low-grade squamous intraepithelial lesion -- very high mag.jpg | LSIL - very high mag. (WC)
</gallery>
<gallery>
Image:Cervical intraepithelial neoplasia (2) koilocytosis.jpg| CIN I. (WC/KGH)
</gallery>
www:
*[http://www.flickr.com/photos/jian-hua_qiao_md/3987000055/ CIN 1 (flickr.com/Qiao)].
*[http://www.eurocytology.eu/static/eurocytology/eng/cervical/mod6img1a.html CIN 1 (eurocytology.eu)].


===High-grade squamous intraepithelial lesion===
===High-grade squamous intraepithelial lesion===
Features - CIN II:<ref name=Ref_PBoD1075-6>{{Ref PBoD|1075-6}}</ref>
{{Main|High-grade squamous intraepithelial lesion}}
*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.
 
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) = 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>
*The difference between CIN II (moderate dysplasia) and CIN III (severe dysplasia) is: changes as in CIN II + outer third (or full thickness).<ref name=Ref_PBoD1075-6>{{Ref PBoD|1075-6}}</ref>
 
DDx:
*[[CIN II]].
*[[Squamous cell carcinoma of the uterine cervix]].
 
====Images====
Image:
<gallery>
Image:Cervical intraepithelial neoplasia (3) CIN2.jpg| CIN II. (WC/KGH)
Image:Cervical_intraepithelial_neoplasia_(4)_CIN3.jpg| CIN III. (WC/KGH)
</gallery>
<gallery>
Image: High-grade squamous intraepithelial lesion -- intermed mag.jpg | HSIL - intermed. mag.
Image: High-grade sqaumous intraepithelial lesion -- high mag.jpg | HSIL - high mag.
Image: High-grade squamous intraepithelial lesion - p16 -- high mag.jpg | HSIL - p16 - high mag.
</gallery>
www:
*[http://www.flickr.com/photos/euthman/6076642630/in/pool-labmed CIN III (flickr.com/euthman)].
*[http://www.flickr.com/photos/euthman/3995927827/in/pool-labmed CIN III (flickr.com/euthman)].
*[http://www.flickriver.com/photos/euthman/tags/hsil/ CIN III - several images (flickriver.com)].


==IHC==
==IHC==
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==Sign-out==
==Sign-out==
{{Main|Low-grade squamous intraepithelial lesion}}
{{Main|High-grade squamous intraepithelial lesion}}
===ECC - cannot grade===
===ECC - cannot grade===
<pre>
<pre>
UTERINE CERVIX, BIOPSY:
UTERINE CERVIX, BIOPSY:
- FRAGEMENTS OF SQUAMOUS EPITHELIUM SHOWING DYSPLASIA, SEE COMMENT.
- FRAGMENTS OF SQUAMOUS EPITHELIUM SHOWING DYSPLASIA, SEE COMMENT.


COMMENT:
COMMENT:
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there is at least low grade-dysplasia. Follow-up is recommended with  
there is at least low grade-dysplasia. Follow-up is recommended with  
re-biopsy if clinically indicated.
re-biopsy if clinically indicated.
</pre>
===LEEP===
<pre>
UTERINE CERVIX, LOOP ELECTROSURGICAL EXCISION PROCEDURE (LEEP):
- CERVICAL INTRAEPITHELIAL NEOPLASIA 2 (MODERATE DYSPLASIA).
- DEEP, ENDOCERVICAL AND EXOCERVICAL MARGINS NEGATIVE FOR INTRAEPITHELIAL NEOPLASIA.
</pre>
<pre>
UTERINE CERVIX, LOOP ELECTROSURGICAL EXCISION PROCEDURE (LEEP):
- CERVICAL INTRAEPITHELIAL NEOPLASIA 3 (SEVERE DYSPLASIA).
- DEEP, ENDOCERVICAL AND EXOCERVICAL MARGINS NEGATIVE FOR INTRAEPITHELIAL NEOPLASIA.
</pre>
<pre>
UTERINE CERVIX, LOOP ELECTROSURGICAL EXCISION PROCEDURE (LEEP):
- CERVICAL INTRAEPITHELIAL NEOPLASIA 3 (SEVERE DYSPLASIA).
- DEEP, ENDOCERVICAL AND EXOCERVICAL MARGINS NEGATIVE FOR INTRAEPITHELIAL NEOPLASIA.
- NEGATIVE FOR MALIGNANCY.
COMMENT:
CIN 3 is seen in 2 of 5 blocks and has a total linear extent of 17 millimeters.
</pre>
<pre>
UTERINE CERVIX, LOOP ELECTROSURGICAL EXCISION PROCEDURE (LEEP):
- HIGH-GRADE SQUAMOUS INTRAEPITHELIAL LESION (HSIL).
- DEEP, ENDOCERVICAL AND EXOCERVICAL MARGINS NEGATIVE FOR DYSPLASIA.
- NEGATIVE FOR MALIGNANCY.
COMMENT:
HSIL is seen in 3 of 4 blocks and has a total linear extent of approximately
12 millimeters.
The HSIL is in keeping with cervical intraepithelial neoplasia 3 (severe dysplasia).
</pre>
===Cervical biopsy===
====LSIL====
<pre>
UTERINE CERVIX, BIOPSY:
- LOW-GRADE SQUAMOUS INTRAEPITHELIAL LESION (LSIL).
- NO ENDOCERVICAL EPITHELIUM IDENTIFIED.
</pre>
<pre>
UTERINE CERVIX, BIOPSY:
- LOW-GRADE SQUAMOUS INTRAEPITHELIAL LESION (LSIL).
- TRANSFORMATION ZONE PRESENT.
</pre>
<pre>
UTERINE CERVIX, BIOPSY:
- LOW-GRADE SQUAMOUS INTRAEPITHELIAL LESION (LSIL).
- CERVICITIS, CHRONIC.
- NO ENDOCERVICAL EPITHELIUM IDENTIFIED.
</pre>
<pre>
UTERINE CERVIX, BIOPSY:
- LOW-GRADE SQUAMOUS INTRAEPITHELIAL LESION (LSIL).
- TRANSFORMATION ZONE PRESENT.
COMMENT:
A p16 stain is patchy and confined mostly to the lower aspect of the squamous epithelium.
</pre>
====CIN 1====
<pre>
UTERINE CERVIX, BIOPSY:
- CERVICAL INTRAEPITHELIAL NEOPLASIA 1 (MILD DYSPLASIA).
- TRANSFORMATION ZONE PRESENT.
</pre>
<pre>
COMMENT:
The Ki-67 positive cells are confined to the lower aspect of the squamous epithelium. 
A p16 stain is negative.
</pre>
====At least CIN 2====
<pre>
UTERINE CERVIX, BIOPSY:
- AT LEAST CERVICAL INTRAEPITHELIAL NEOPLASIA 2 (MODERATE DYSPLASIA).
- TRANSFORMATION ZONE PRESENT.
</pre>
</pre>


<pre>
<pre>
UTERINE ENDOCERVIX, CURETTAGE:
UTERINE ENDOCERVIX, CURETTAGE:
- HIGH-GRADE SQUAMOUS INTRAEPITHELIAL LESION (HSIL).
- FRAGMENTS OF SQUAMOUS EPITHELIUM SHOWING DYSPLASIA, CANNOT GRADE, SEE COMMENT.
- ENDOCERVICAL MUCOSA AND STRIPPED ENDOCERVICAL EPITHELIUM WITHIN NORMAL LIMITS.
- BENIGN STRIPPED ENDOCERVICAL EPITHELIUM AND BENIGN SCANT ENDOCERVICAL MUCOSA.
 
COMMENT:
The HSIL is in keeping with CIN 2.
</pre>
 
<pre>
UTERINE CERVIX, BIOPSY:
- HIGH-GRADE SQUAMOUS INTRAEPITHELIAL LESION (HSIL).
- TRANSFORMATION ZONE PRESENT.


COMMENT:
COMMENT:
A p16 stain is strong and within the limits of the tissue orientation appears to mark the
The fragments of squamous epithelium do not show the full epithelial thickness; this limits
full thickness of squamous epithelium. A Ki-67 stain marks increased numbers of superficial
the interpretation.
epithelial cells.
 
The HSIL is in keeping with at least CIN 2.
</pre>


====CIN 3====
A p16 immunostain strongly marks very scant squamous epithelium, and a Ki-67 immunostain
<pre>
marks increased numbers of squamous cells.  
UTERINE CERVIX, BIOPSY:
- CERVICAL INTRAEPITHELIAL NEOPLASIA 3 (SEVERE DYSPLASIA).
</pre>


<pre>
A cervical biopsy is suggested.
COMMENT:
A p16 stain marks the full thickness of the squamous epithelium and is strong. 
A Ki-67 stain marks increased numbers of superficial epithelial cells.
</pre>
</pre>
===Micro===
====CIN 1====
The sections show the transformation zone. The squamous epithelium has cells with an increased nuclear size, nuclear hyperchromasia, perinuclear clearing and irregularities in the nuclear membrane. The nucleus-to-cytoplasm ratio is mildly increased. Occasional binucleation is identified. Mitoses are seen in the low third of the epithelium. Nucleoli are not apparent. No columnar dysplasia is identified.
====CIN 3====
The sections show the transformation zone.
The squamous epithelium has an increased nuclear-cytoplasmic ratio, loss of polarity, mitoses and nuclear hyperchromasia extending to the superficial third of the epithelium.  Mitoses are seen in the upper third of the epithelium.  No nucleoli are present. No invasion is identified.
The columnar epithelium has focal involvement by the squamous lesion.  There is no columnar dysplasia.  The margins are negative for dysplasia.
=====Biopsy=====
The sections show the transformation zone.
The squamous epithelium has an increased nuclear-cytoplasmic ratio, loss of polarity,
mitoses and nuclear hyperchromasia extending to the superficial third of the epithelium.
Mitoses are seen in the upper third of the epithelium. Nucleoli are not apparent.
No invasion is identified.
No columnar dysplasia is identified.
=====Alternate=====
The sections show fragments of transformation zone.
There is dysplastic squamous epithelium with coarse chromatin, nuclear hyperchromasia,
nuclear enlargement, irregular nuclear membranes, and an increase nuclear-to-cytoplasmic
ratio.  Mitotic activity is abundant focally (5 mitoses/0.2376 mm*mm).  The dysplastic
squamous epithelium does not show appreciable maturation toward the surface (CIN 3).
The dysplastic squamous epithelium is not associated with stroma; thus, the
presence/absence of invasion cannot be assessed.  Small nucleoli are seen rarely.
There is benign squamous epithelium. Scant benign stripped endocervical epithelium is
present.


==See also==
==See also==
Michael
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