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Avoidance of over-reporting of atypical/borderline cytology

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Atypical squamous cells of undetermined significance (ASC-US)

  • ASC-US (or borderline changes in squamous cells) border on LSIL and can largely be resolved by HPV triage. 
  • HPV negativity would usually exclude minor changes in mature or intermediate squamous cells without koilocytosis (the only diagnostic feature of HPV infection). 
  • Minor nuclear enlargement and hyperchromasia is frequent in peri-menopausal women but may end up being reported as ASC-US. 
  • Minor changes of HPV, confirmed on high-risk HPV triage, should be managed by investigation if they persist as for LSIL.

Figure 10.9 Examples of ASC-US bordering on normality and LSIL 


How to avoid unnecessary ASC-US reports

  • ASC-US can be controlled by HPV triage because most reactive changes will be negative
  • Monitoring HSIL, LSIL and ASC rates forms a useful method of quality assurance
  • Genuine uncertainty must be acknowledged by investigation of atypical cases
  • Multidisciplinary discussion and slide review can avoid unnecessary treatment


Atypical squamous cells, cannot exclude HSIL (ASC-H)

  • The whole slide should be examined carefully to look for recognizable HSIL to avoid unnecessary ASC-H reports.
  • ASC-H is reported when features of HSIL are uncertain after consideration of all the conditions discussed above as potential false negatives and false positives. 
  • It is easy to see how Figures 10.1 (b), 10.2 (a-b) and 10.3 (a-c) could have been reported as ASC-H if these cells were representative of the most abnormal cells on the slide.  Indeed, some of them were reported as ASC-H, which may avoid false negative reports in difficult cases. 
  • Equally, in some examples of immature squamous metaplasia, tubal metaplasia and lower uterine segment sampling it may be difficult in practice to avoid an ASC-US or ASC-H report – as in Figures 10.5 (c-d), 10.6 (b), 10.8 (b) and 10.9 (b).
  • Colposcopy and slide review of cytology and histology can avoid unnecessary treatment in potential false positive cytology cases. 
  • Monitoring HSIL rates for laboratories and individuals can be used as a method of quality control. 


Atypical glandular cells (AGC)

AGC presents a two-fold problem in the context of false negatives and false positives:

  1. Distinguishing benign or metaplastic processes from neoplastic glandular cells as in Figure 10.11 (a-b).
  2. Distinguishing reactive glandular cells from HSIL as in Figure 10.5 (c).

Classical features of AIS must be distinguished from reactive endocervical cells, tubal metaplasia and TEM by attention to the chromatin pattern, palisading arrangement of cells and absence of stromal cells or cilia. 

Clinico-pathological correlation and slide review before treatment is the key to avoiding over- or under-treatment of ‘difficult’ glandular abnormalities.


Figure 10.11 Atypical glandular cells favour neoplasia

(a) Tubal metaplasia mimicking AIS but with regular chromatin and even nuclear membranes
(b) AIS represented by this group of cells only. 
(c) AIS in SurePath.


How to avoid unnecessary ASC-H and AGL reports

  • Search the slide for more obvious HSIL or CGIN before reporting the slide
  • Discuss difficult cases with colleagues before sending out ASC-H or AGL reports
  • Colposcopy and multidisciplinary review of histology and cytology slides can avoid unnecessary treatment in atypical cases
  • Remember that judicious use of ASC-H and AGL categories can avoid false positives and false negatives


Learning points from Chapter 10

  1. Dyskaryosis should be present in all false negative and absent in all false positive cellular abnormalities (at least on review)
  2. ASC and AGL (borderline) reports should only be used for genuine doubt between negative/reactive and SIL/neoplasia
  3. False negatives can be avoided by familiarity with their main causes: sparse, pale and small cell dyskaryosis, hyperchromatic crowded cell groups, and dyskaryosis masked by inflammation
  4. Hyperchromatic crowded cell groups and sparse dyskaryotic cells are potential false negatives in LBC as well as conventional smears
  5. False positives may be avoided by familiarity with the full spectrum of reactive changes in metaplastic and inflammatory conditions
  6. Endocervicitis, atrophic vaginitis, immature squamous metaplasia, tubal metaplasia and tuboendometrioid metaplasia are important potential false positives
  7. False positives are important because unnecessary excision biopsy may increase risk of premature rupture of membranes in pregnancy
  8. Atypical/borderline reports when used in cases of genuine doubt may avoid false negatives and false positives