Biopsy: histologic analysis confirms the presence or absence of disease

Biopsy is used to obtain samples from tissue that, through prior testing, has been definitively determined to be abnormal or highly suspicious. Histologic analysis can confirm these findings, better characterize the abnormalities, and help direct appropriate intervention. A biopsy may also be taken as part of treatment for pre-cancerous or cancerous lesions.¹

In a biopsy, a small sample of tissue (about 4 to 5 mm) is removed from abnormal areas of the cervix. This sample includes more than the epithelial cells collected for cytology, extending to the bottom layer of cervical squamous epithelial tissue and usually into the underlying stroma.

Tissue samples are typically prepared with hematoxylin and eosin (H&E) stain and examined using a microscope to identify abnormal patterns of cell growth.

Interest is growing in the ability to stain for other intracellular proteins that are more specific to cervical oncogenesis and that pathologists can interpret more definitively than H&E staining.

Classifying pre-cancer

Explore different histologies of cervical tissue

types_of_cervical_intraepithelial_neoplasia

Low-grade dysplasia

Basaloid cells invade lower third of epithelium

High-grade dysplasia

Basaloid cells invade lower third to two-thirds of epithelium

High-grade dysplasia

Basaloid cells invade two-thirds up to the full thickness of the epithelium

H&E stained samples at 40x magnification.

Since the 1980s, cervical intraepithelial neoplasia (CIN) have been classified into three categories²:

CIN 1 = mild dysplasia
CIN 2 = moderate dysplasia
CIN 3 = both severe dysplasia and carcinoma in situ

The key criterion for differentiating among these categories is the amount of tissue comprised of atypical basaloid cells, which is related to progressive loss in the ability of cells to mature and differentiate into normal epithelial layers.²

mechanism_of_HPV_infection

HPV infection involves the introduction of viral DNA into cervical basal cells. The virus replicates in the differentiated outer cell layers and new infectious particles are produced.²

Persistent high-risk HPV (hrHPV) infection may cause cells to transform and become pre-cancerous: the cell cycle is disrupted and the cells divide or proliferate abnormally.²

Ultimately, invasive cancer can occur when these transformed cells perforate the basal membrane.

In CIN 1, atypical basaloid (basal-like) cells occupy the lower third of the epithelium, in CIN 2 they occupy the lower third to two-thirds, and in CIN 3 they occupy two-thirds to the full epithelium.²

More recently, a two-tiered system has been recommended for histology findings.

This uses the same terms found in the Bethesda cytology categories, and thus can provide better continuity and consistency among cytologists, pathologists, and, ultimately, clinicians. The system distinguishes abnormal findings as³:

Low-grade squamous intraepithelial lesion (LSIL) (CIN 1)
High-grade squamous intraepithelial lesion (HSIL) (CIN 2 and CIN 3)

A key rationale for this classification is that it more accurately captures the substantial virologic and molecular difference between LSIL and HSIL, while reflecting clinical evidence that shows the difficulty in reproducibly subdividing HSIL into moderate and severe dysplasia (CIN 2, CIN 3).³

Cervical Cancer Biomarkers Learning Center

Biopsy: histologic analysis confirms the presence or absence of disease

Classifying pre-cancer

Explore different histologies of cervical tissue

References