Cervical dysplasia

Author: Mikael Häggström

Presentations

Cervical dysplasia specimens may present as:

• Cervical biopsy
• Cervical cone
• Hysterectomy

Microscopic evaluation

Dysplasia is mainly seen as nuclei with hyperchromasia, coarse chromatin and irregular contours.

Dysplasia grading

Cervical intraepithelial neoplasia

Histology Grade	Corresponding Cytology	Description	Image
CIN 1 (Grade I)	Low-grade squamous intraepithelial lesion (LSIL)	Mild epithelial dysplasia Confined to the basal 1/3 of the epithelium
CIN 2/3	High-grade squamous intraepithelial lesion (HSIL)	Represents a mix of low and high-grade lesions not easily differentiated by histology
CIN 2 (Grade II)		Moderate dysplasia confined to the basal 2/3 of the epithelium
CIN 3 (Grade III)		Severe dysplasia with undifferentiated neoplastic cells that span more than 2/3 of the epithelium May involve the full thickness May also be referred to as cervical carcinoma in situ
Invasive squamous- cell carcinoma of the cervix		Infiltration as irregular anastomosing nests or single cells.

• 
  Spectrum from normal to high grade SIL.
• 
  Endocervical gland invasion is associated with high-grade lesions.
• 
  Invasive cervical cancer is most commonly squamous cell carcinoma (about 80–85% of cervical cancers). In contrast to tangentially cut projections of glands involved by HSIL, the invasive nests of tumor cells are irregular and accompanied by a distinct stromal reaction of edema and chronic inflammatory cells.

Radicality

Locations of non-radicality should be reported in relation to tissue markings (such as needles), or in terms of quadrants or corresponding to a clock face, based on the patient being in supine position.

Look whether there is normal epithelium on each side of all slices where neoplasia is seen, and when the epithelium is missing in any direction, consider ordering additional serial sections or step sections.

HPV changes

Also look koilocytic changes of human papillomavirus (HPV), with such cells typically displaying:

• Nuclear enlargement (two to three times normal size).
• Irregularity of the nuclear membrane contour, creating a wrinkled or raisinoid appearance.
• A darker than normal staining pattern in the nucleus, known as hyperchromasia.
• Perinuclear cytoplasmic vacuolization ("nuclear halo").

p16 immunostaining

p16 staining. To support a diagnosis of high-grade SIL, the reaction needs to be strong and diffuse, as seen here.

Invasive cervical squamous cell carcinoma on H&E histopathology and Ki-67 immunohistochemistry. The latter correlates well with the degree and level of dysplasia.

Indications for p16 immunostaining are:

• To differentiate between HSIL and mimics such as atrophy, immature squamous metaplasia, or tangential cuts.
• If a diagnosis of cervical intraepithelial neoplasia grade 2 (CIN2) is considered
• In case of professional disagreement.
• Cases of high-risk colposcopic referral situations where the H&E biopsy specimen is interpreted as LSIL or lower.

Microscopy report

If a neoplasia is found, the report should include:

• The histolopathological type and degree of differentiation
• Location and extent, if possible (generally not on biopsies)
• Radicality, if possible (generally not in biopsies)

High-grade squamous intraepithelial lesion (CIN-2), present at 3:00 to 12:00. All margins of excision are negative for CIN-2. Example microscopic description The transition zone has thickened endocervical epithelium with poorly differentiated neoplastic cells, which span more than half of the epithelial thickness, and with invasion of endocervical glands. Otherwise, glands are clad by a simple columnar epithelium without atypia. The neoplastic cells are radically removed.

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