Squamous intraepithelial lesion of the uterine cervix

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Squamous intraepithelial lesion of the uterine cervix is a precancerous lesion of the uterine cervix.

It is generally referred to as squamous intraepithelial lesion, abbreviated SIL, though this is somewhat ambiguous as other non-cervical sites are increasingly using the terminology.

In the past, it was known as cervical intraepithelial neoplasia, abbreviated CIN. Prior to that, it was known as cervical dysplasia.

General

  • Refers to changes in squamous epithelium.

Grades (squamous intraepithelial neoplasia):

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

Bethesda system:

Treatment

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

Loop electrosurgical excision procedure (LEEP):

  • 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.

Gross

  • Acetowhite lesion at colposcopy.

Microscopic

Cervical intraepithelial neoplasia I

Features - Cervical intraepithelial neoplasia (CIN) I:[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]

Image

  • CIN I. (WC/KGH)

www:

Cervical intraepithelial neoplasia II

Features - CIN II:[1]

  • 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.

Image:

  • CIN I. (WC/KGH)

Cervical intraepithelial neoplasia III

Features - CIN III:[1]

  • Same changes as in CIN II + outer third (or full thickness).

Notes:

  1. Hyperchromasia is a very useful feature for identifying CIN (particularly at low power, i.e. 25x).
  2. Koilocytes are the key feature of CIN I.
  3. Koilocytes are not considered to be part of a CIN II lesion or CIN III lesion.
  4. Large irregular nuclei are not required for CIN II... but you should think about it.
  5. Some mild changes at the squamo-columnar junction are expected.
  6. 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.
  7. Prominent nucleoli are not present in CIN.[2]
    • Nucleoli are common in reactive changes.[4]
  8. The most probably place for CIN is the posterior cervix (6 o'clock position) - risk is marginally increased.[5]

DDx:

Images

  • CIN I. (WC/KGH)

www:

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. [6]
    • 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.

IHC

Features:[7]

  • 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.[8]
    • CIN I with p16 staining appears to have a higher risk of progression the p16 negative CIN I.[9]

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.

LEEP

UTERINE CERVIX, LOOP ELECTROSURGICAL EXCISION PROCEDURE (LEEP):
- CERVICAL INTRAEPITHELIAL NEOPLASIA 2 (MODERATE DYSPLASIA).
- DEEP, ENDOCERVICAL AND EXOCERVICAL MARGINS NEGATIVE FOR INTRAEPITHELIAL NEOPLASIA.

UTERINE CERVIX, LOOP ELECTROSURGICAL EXCISION PROCEDURE (LEEP):
- CERVICAL INTRAEPITHELIAL NEOPLASIA 3 (SEVERE DYSPLASIA).
- DEEP, ENDOCERVICAL AND EXOCERVICAL MARGINS NEGATIVE FOR INTRAEPITHELIAL NEOPLASIA.

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.

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).

Biopsy

LSIL

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.

At least CIN 2

UTERINE CERVIX, BIOPSY:
- AT LEAST CERVICAL INTRAEPITHELIAL NEOPLASIA 2 (MODERATE DYSPLASIA).
- TRANSFORMATION ZONE PRESENT.

UTERINE ENDOCERVIX, CURETTAGE:
- HIGH-GRADE SQUAMOUS INTRAEPITHELIAL LESION (HSIL).
- ENDOCERVICAL MUCOSA AND STRIPPED ENDOCERVICAL EPITHELIUM WITHIN NORMAL LIMITS.

COMMENT:
The HSIL is in keeping with CIN 2.

CIN 3

UTERINE CERVIX, BIOPSY:
- CERVICAL INTRAEPITHELIAL NEOPLASIA 3 (SEVERE DYSPLASIA).

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.

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

References

  1. ↑ 1.0 1.1 1.2 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. ↑ 2.0 2.1 2.2 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.
  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. ↑ STC. January 2009.
  5. ↑ Pretorius, RG.; Zhang, X.; Belinson, JL.; Zhang, WH.; Ren, SD.; Bao, YP.; Qiao, YL. (Jan 2006). "Distribution of cervical intraepithelial neoplasia 2, 3 and cancer on the uterine cervix.". J Low Genit Tract Dis 10 (1): 45-50. PMID 16378031.
  6. ↑ V. Dube 2008.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
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