Low-grade squamous intraepithelial lesion: Difference between revisions

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{{ Infobox diagnosis
| Name      = {{PAGENAME}}
| Image      = Low-grade squamous intraepithelial lesion -- high mag.jpg
| Width      =
| Caption    = LSIL. [[H&E stain]].
| Synonyms  =
| Micro      = nuclear membrane irregularies, nuclear hyperchromasia, +/-clear perinuclear halos (koilocytic change), +/-nuclear enlargement, large [[NC ratio]] (usually ~ 1:3), +/-mitoses (lower third)
| Subtypes  =
| LMDDx      = [[high-grade squamous intraepithelial lesion]], [[squamous metaplasia of the uterine cervix|squamous metaplasia]], [[reactive squamous epithelium of the uterine cervix|reactive changes]], normal cervix
| Stains    =
| IHC        = p16 -ve (or lower 1/3 +ve), Ki-67 occasional cells - lower half
| EM        =
| Molecular  =
| IF        =
| Gross      =
| Grossing  =
| Site      = [[uterine cervix]]
| Assdx      =
| Syndromes  =
| Clinicalhx =
| Signs      = [[acetowhite lesion]]
| Symptoms  =
| Prevalence = common
| Bloodwork  =
| Rads      =
| Endoscopy  =
| Prognosis  = benign, usually regresses
| Other      =
| ClinDDx    = [[squamous metaplasia of the uterine cervix|squamous metaplasia]]
| Tx        = follow-up - unless persistent
}}
'''Low-grade squamous intraepithelial lesion''', abbreviated '''LSIL''', is a pre-cancerous lesions of the [[uterine cervix]].
'''Low-grade squamous intraepithelial lesion''', abbreviated '''LSIL''', is a pre-cancerous lesions of the [[uterine cervix]].


Increasingly, the term is being applied to other anatomical sites, e.g. [[vagina]].
Increasingly, the term is being applied to other anatomical sites, e.g. [[vagina]], [[anal intraepithelial lesions|anus]].


It is in the larger category of '''[[Squamous intraepithelial lesion of the uterine cervix|squamous intraepithelial lesion]]''', abbreviated '''SIL'''.
It is in the larger category of '''[[Squamous intraepithelial lesion of the uterine cervix|squamous intraepithelial lesion]]''', abbreviated '''SIL'''.
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Overview:
Overview:
*[[LSIL]]: follow-up unless persistent. It usually regresses on its own.   
*[[LSIL]]: follow-up unless persistent. It usually regresses on its own.   
==Gross==
*[[Acetowhite epithelium|Acetowhite lesion]].<ref name=pmid19256708>{{Cite journal  | last1 = Li | first1 = W. | last2 = Venkataraman | first2 = S. | last3 = Gustafsson | first3 = U. | last4 = Oyama | first4 = JC. | last5 = Ferris | first5 = DG. | last6 = Lieberman | first6 = RW. | title = Using acetowhite opacity index for detecting cervical intraepithelial neoplasia. | journal = J Biomed Opt | volume = 14 | issue = 1 | pages = 014020 | month =  | year =  | doi = 10.1117/1.3079810 | PMID = 19256708 }}</ref>


==Microscopic==
==Microscopic==
Features:<ref name=Ref_PBoD1075-6>{{Ref PBoD|1075-6}}</ref>
Features:<ref name=Ref_PBoD1075-6>{{Ref PBoD|1075-6}}</ref>
*"Koilocytic atypia":<ref name=Ref_GP146>{{Ref GP|146}}</ref>
*"Koilocytic atypia":<ref name=Ref_GP146>{{Ref GP|146}}</ref>
**Cytoplasmic halos.
**Clear cytoplasmic halos (perinuclear clearing).
**Nuclear enlargement >=3:1 enlarged nucleus:normal nucleus.
**Nuclear enlargement.
**Nuclear membrane irregularities.
***Classically >=3:1 enlarged nucleus:normal nucleus.
**Nuclear hyperchromasia.
***May be mild (superficial cells = size of basal cells).
**Nuclear membrane irregularities - '''important'''.
**Nuclear hyperchromasia - '''important'''.
**Coarse chromatin.
**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>
**+/-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>
***Useful when present.


Note:
Note:
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DDx:
DDx:
*[[High-grade squamous intraepithelial lesion]].
*[[High-grade squamous intraepithelial lesion]].
*[[Uterine cervix with reactive changes]].
*[[Squamous metaplasia of the uterine cervix]].
*[[Reactive squamous epithelium of the uterine cervix]].
*Normal cervix.


===Koilocytes versus benign squamous===
===Koilocytes versus benign squamous===
Koilocytes:
Koilocytes:
*Perinuclear clearing.
*Perinuclear clearing.
*Nuclear changes.  
**Halo should be crystal clear.
*Nuclear changes - '''key feature'''.  
**Size similar (or larger) to those in the basal layer of the epithelium.
**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>
***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.
**Nuclear hyperchromasia.
 
**Central location - nucleus should be in the middle of the cell.
Notes:
***Benign cells have a small nucleus that is peripheral.
# Both perinuclear clearing and nuclear changes are essential.
# Benign cells have a small nucleus that is peripheral.


===Images===
===Images===
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www:
www:
*[http://www.flickr.com/photos/jian-hua_qiao_md/3987000055/ CIN 1 (flickr.com/Qiao)].
*[http://www.flickr.com/photos/jian-hua_qiao_md/3987000055/ CIN 1 (flickr.com/Qiao)].
*[https://www.flickr.com/photos/jian-hua_qiao_md/3986999903/ CIN 1 (flickr.com/Qiao)].
*[http://www.eurocytology.eu/static/eurocytology/eng/cervical/mod6img1a.html CIN 1 (eurocytology.eu)].
*[http://www.eurocytology.eu/static/eurocytology/eng/cervical/mod6img1a.html CIN 1 (eurocytology.eu)].


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*Both p16 and Ki-67 are usually negative in CIN I -- 75% of cases.<ref name=pmid22104735>{{Cite journal  | last1 = Jackson | first1 = JA. | last2 = Kapur | first2 = U. | last3 = Erşahin | first3 = Ç. | title = Utility of p16, Ki-67, and HPV test in diagnosis of cervical intraepithelial neoplasia and atrophy in women older than 50 years with 3- to 7-year follow-up. | journal = Int J Surg Pathol | volume = 20 | issue = 2 | pages = 146-53 | month = Apr | year = 2012 | doi = 10.1177/1066896911427703 | PMID = 22104735 }}</ref>
*Both p16 and Ki-67 are usually negative in CIN I -- 75% of cases.<ref name=pmid22104735>{{Cite journal  | last1 = Jackson | first1 = JA. | last2 = Kapur | first2 = U. | last3 = Erşahin | first3 = Ç. | title = Utility of p16, Ki-67, and HPV test in diagnosis of cervical intraepithelial neoplasia and atrophy in women older than 50 years with 3- to 7-year follow-up. | journal = Int J Surg Pathol | volume = 20 | issue = 2 | pages = 146-53 | month = Apr | year = 2012 | doi = 10.1177/1066896911427703 | PMID = 22104735 }}</ref>
**CIN I with p16 staining appears to have a higher risk of progression the p16 negative CIN I.<ref name=pmid19683687>{{Cite journal  | last1 = del Pino | first1 = M. | last2 = Garcia | first2 = S. | last3 = Fusté | first3 = V. | last4 = Alonso | first4 = I. | last5 = Fusté | first5 = P. | last6 = Torné | first6 = A. | last7 = Ordi | first7 = J. | title = Value of p16(INK4a) as a marker of progression/regression in cervical intraepithelial neoplasia grade 1. | journal = Am J Obstet Gynecol | volume = 201 | issue = 5 | pages = 488.e1-7 | month = Nov | year = 2009 | doi = 10.1016/j.ajog.2009.05.046 | PMID = 19683687 }}</ref>
**CIN I with p16 staining appears to have a higher risk of progression the p16 negative CIN I.<ref name=pmid19683687>{{Cite journal  | last1 = del Pino | first1 = M. | last2 = Garcia | first2 = S. | last3 = Fusté | first3 = V. | last4 = Alonso | first4 = I. | last5 = Fusté | first5 = P. | last6 = Torné | first6 = A. | last7 = Ordi | first7 = J. | title = Value of p16(INK4a) as a marker of progression/regression in cervical intraepithelial neoplasia grade 1. | journal = Am J Obstet Gynecol | volume = 201 | issue = 5 | pages = 488.e1-7 | month = Nov | year = 2009 | doi = 10.1016/j.ajog.2009.05.046 | PMID = 19683687 }}</ref>
==Sign-out==
===ECC - cannot grade===
<pre>
UTERINE CERVIX, BIOPSY:
- FRAGMENTS OF SQUAMOUS EPITHELIUM SHOWING DYSPLASIA, SEE COMMENT.
COMMENT:
The fragments of squamous epithelium do not show full epithelial
thickness. Thus, while dysplasia is apparent, it is not possible
to distinguish low-grade from high-grade in this specimen. That said,
there is at least low grade-dysplasia. Follow-up is recommended with
re-biopsy if clinically indicated.
</pre>
===Biopsy - cannot grade===
<pre>
UTERINE CERVIX, BIOPSY:
- AT LEAST LOW-GRADE SQUAMOUS INTRAEPITHELIAL LESION (LSIL), SEE COMMENT.
- BENIGN ENDOCERVICAL EPITHELIUM.
COMMENT:
A concerning area of dysplastic squamous epithelium is missing its surface cells. This
precludes assessment for a high-grade lesion. Follow-up is recommended with
re-biopsy if clinically indicated.
</pre>
===Cervical biopsy===
<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>
<pre>
COMMENT:
A p16 immunostain is strong and diffuse in the lower aspect of squamous epithelium,
and weak and patchy in the superficial portions; this is compatible with LSIL.
</pre>
===Micro===
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.


==See also==
==See also==
*[[Squamous intraepithelial lesion of the uterine cervix|Squamous intraepithelial lesion]].
*[[Squamous intraepithelial lesion of the uterine cervix|Squamous intraepithelial lesion]].
*[[Uterine cervix]]
*[[Uterine cervix]].
*[[Gynecologic cytopathology]].
*[[Gynecologic cytopathology]].


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
==External links==
*[http://www.medecine.ups-tlse.fr/dcem1/histologie/courtade/CINtec.pdf Interpretation altas for p16 staining (ups-tlse.fr)].


[[Category:Uterine cervix]]
[[Category:Uterine cervix]]
[[Category:Diagnosis]]
[[Category:Diagnosis]]
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