Low-grade squamous intraepithelial lesion

Low-grade squamous intraepithelial lesion
	Diagnosis in short
	; LSIL. H&E stain.
LM	nuclear membrane irregularies, nuclear hyperchromasia, +/-clear perinuclear halos (koilocytic change), +/-nuclear enlargement, large NC ratio (usually ~ 1:3), +/-mitoses (lower third)
LM DDx	high-grade squamous intraepithelial lesion
IHC	p16 -ve (or lower 1/3 +ve), Ki-67 occasional cells - lower half
Site	uterine cervix
Signs	acetowhite positive lesion
Prevalence	common
Prognosis	benign, usually regresses
Clin. DDx	squamous metaplasia
Treatment	follow-up - unless persistent

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.

It is in the larger category of squamous intraepithelial lesion, abbreviated SIL.

General

Precursor lesion of cervical squamous cell carcinoma.
Usually associated with human papilloma virus.

SIL is divided into grades:

Low-grade.
High-grade.

The new and old terminology

SIL (current terminology)	LSIL	HSIL
Recent terminology	CIN I	CIN II, CIN III
Very old terminology	mild dysplasia	moderate dysplasia, severe dysplasia

Treatment

Overview:

LSIL: follow-up unless persistent. It usually regresses on its own.

Microscopic

Features:^[1]

"Koilocytic atypia":^[2]
- 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).^[3]

Note:

Atypical cells usually close to basement membrane.
- May be seen, focally, in the upper layers.^[2]

DDx:

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. ^[4]
- 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

LSIL - intermed. mag. (WC)
LSIL - intermed. mag. (WC)
LSIL - high mag. (WC)
LSIL - very high mag. (WC)

CIN I. (WC/KGH)

www:

IHC

Features:^[5]

p16.
- Diffuse strong staining involving at least all of the basal aspect of the epithelium = CIN II or CIN III.
- Patchy, weak positive staining = CIN I or squamous metaplasia.
Ki-67.
- Several positive cells above basal layer suggests CIN II or CIN III.

Notes:

Both p16 and Ki-67 are usually negative in CIN I -- 75% of cases.^[6]
- CIN I with p16 staining appears to have a higher risk of progression the p16 negative CIN I.^[7]

Sign-out

ECC - cannot grade

UTERINE CERVIX, BIOPSY:
- FRAGEMENTS 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.

Cervical biopsy

UTERINE CERVIX, BIOPSY:
- LOW-GRADE SQUAMOUS INTRAEPITHELIAL LESION (LSIL).
- NO ENDOCERVICAL EPITHELIUM IDENTIFIED.

UTERINE CERVIX, BIOPSY:
- LOW-GRADE SQUAMOUS INTRAEPITHELIAL LESION (LSIL).
- TRANSFORMATION ZONE PRESENT.

UTERINE CERVIX, BIOPSY:
- LOW-GRADE SQUAMOUS INTRAEPITHELIAL LESION (LSIL).
- CERVICITIS, CHRONIC.
- NO ENDOCERVICAL EPITHELIUM IDENTIFIED.

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.

CIN 1

UTERINE CERVIX, BIOPSY:
- CERVICAL INTRAEPITHELIAL NEOPLASIA 1 (MILD DYSPLASIA).
- TRANSFORMATION ZONE PRESENT.

COMMENT:
The Ki-67 positive cells are confined to the lower aspect of the squamous epithelium.  
A p16 stain is negative.

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.

References

↑ 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.
↑ ^2.0 ^2.1 Nucci, Marisa R.; Oliva, Esther (2009). Gynecologic Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 146. ISBN 978-0443069208.
↑ 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.
↑ V. Dube 2008.
↑ Singh, M.; Mockler, D.; Akalin, A.; Burke, S.; Shroyer, A.; Shroyer, KR. (Feb 2012). "Immunocytochemical colocalization of P16(INK4a) and Ki-67 predicts CIN2/3 and AIS/adenocarcinoma.". Cancer Cytopathol 120 (1): 26-34. doi:10.1002/cncy.20188. PMID 22162342.
↑ Jackson, JA.; Kapur, U.; Erşahin, Ç. (Apr 2012). "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.". Int J Surg Pathol 20 (2): 146-53. doi:10.1177/1066896911427703. PMID 22104735.
↑ del Pino, M.; Garcia, S.; Fusté, V.; Alonso, I.; Fusté, P.; Torné, A.; Ordi, J. (Nov 2009). "Value of p16(INK4a) as a marker of progression/regression in cervical intraepithelial neoplasia grade 1.". Am J Obstet Gynecol 201 (5): 488.e1-7. doi:10.1016/j.ajog.2009.05.046. PMID 19683687.

[Ref_PBoD1075-6-1] 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.

[Ref_GP146-2] 2.0 ^2.1 Nucci, Marisa R.; Oliva, Esther (2009). Gynecologic Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 146. ISBN 978-0443069208.

[pmid11491378-3] 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] V. Dube 2008.

[pmid22162342-5] Singh, M.; Mockler, D.; Akalin, A.; Burke, S.; Shroyer, A.; Shroyer, KR. (Feb 2012). "Immunocytochemical colocalization of P16(INK4a) and Ki-67 predicts CIN2/3 and AIS/adenocarcinoma.". Cancer Cytopathol 120 (1): 26-34. doi:10.1002/cncy.20188. PMID 22162342.

[pmid22104735-6] Jackson, JA.; Kapur, U.; Erşahin, Ç. (Apr 2012). "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.". Int J Surg Pathol 20 (2): 146-53. doi:10.1177/1066896911427703. PMID 22104735.

[pmid19683687-7] Pino, M.; Garcia, S.; Fusté, V.; Alonso, I.; Fusté, P.; Torné, A.; Ordi, J. (Nov 2009). "Value of p16(INK4a) as a marker of progression/regression in cervical intraepithelial neoplasia grade 1.". Am J Obstet Gynecol 201 (5): 488.e1-7. doi:10.1016/j.ajog.2009.05.046. PMID 19683687.

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