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Atypical and borderline changes

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Definitions of ‘borderline’ and ‘atypical’

In the BSCC classification “The term BNC [borderline nuclear change] is used as a holding category when there is genuine doubt as to whether or not the changes are neoplastic.” (Denton et al. 2008).

Since the Bethesda system was first introduced (Kurman & Solomon 1988) the category ‘atypical cells of undetermined significance’ (ASCUS) has included “cells for which a reliable interpretation of SIL cannot be made although the cells contain features that are more marked than merely reactive changes”.

Thus the original definitions for these words are sufficiently similar for them to be regarded as synonyms. 

Atypical squamous cells (ASC) are now subdivided into the majority that border on LSIL, defined as ASC of undetermined significance (ASC-US), and a minority in which the changes ‘cannot exclude HSIL’ (ASC-H). (Nayar & Solomon 2004).

The BSCC system defines ‘borderline changes in squamous cells, not otherwise specified (NOS)’ as the same as ASC-US and recognises a smaller group of borderline changes in which ‘high-grade dyskaryosis cannot be excluded’, which warrant immediate referral for colposcopy. 

The words ‘borderline’ and ‘atypical’ are used when there is genuine doubt as to whether the changes are neoplastic or reactive

While ASC-US and borderline changes border on LSIL, a minority, defined as ASC-H, cannot exclude HSIL or cancer


ASC-US / borderline changes in squamous cells, NOS

In the majority of cytological preparations, an experienced cytotechnologist or pathologist can make the distinction between benign epithelial cells and LSIL with sufficient confidence to issue a definitive report. 

There are two situations in which the ASC-US category applies:

  • Cytoplasmic changes suggesting HPV effect with minimal nuclear change.
  • Cytological preparations in which it is genuinely difficult to distinguish benign, reactive or degenerative nuclear changes from LSIL


ASC-H / borderline changes, high-grade dyskaryosis not excluded.

These terms are used for changes, often in very few cells, where it is difficult to distinguish benign reactive or metaplastic changes from HSIL, AIS or even invasive cancer.

The commonest reasons for this problem are the distinction of i) immature squamous metaplasia from HSIL/moderate dysplasia/dyskaryosis, and ii) hyperchromatic crowded cell groups of metaplastic or glandular cells from HSIL/severe dyskaryosis or AIS. 

In the majority of cytological preparations, an experienced cytotechnologist or pathologist can make the distinction between benign epithelial cells and LSIL, HSIL, AIS or cancer with sufficient confidence to issue a definitive report.


AGC / borderline changes in endocervical cells

Glandular cells may present a particular difficulties in cytology in the i) the distinction of benign from neoplastic endocervical cells, ii) the distinction of neoplastic endocervical cells (AIS) from HSIL and iii) the recognition of benign and neoplastic changes in non-cervical glandular cells including endometrial cells. 

Table 9b-1. Simplified correlation of the Bethesda, UK and Australian modified Bethesda system for atypical /borderline cytology 


Atypical squamous cells

Atypical glandular cells

The Bethesda system




AGC favour neoplasia

The UK system

Borderline changes in squamous cells NOS

Borderline changes, high-grade dyskaryosis not excluded

Borderline changes in endocervical cells

Modified Bethesda system (Australia)

Possible LSIL

Possible HSIL

Atypical endocervical cells of undetermined significance

Atypical glandular cells of undetermined significance


ASC-US, atypical squamous cells of undetermined significance; ASC-H, atypical squamous cells cannot exlude HSIL; LSIL, low-grade squamous intraepithelial lesion; HSIL, high-grade squamous intraepithelial lesion; NOS, not otherwise specified.