Cytology after radical trachelectomy for cervical cancer

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Cytology after radical trachelectomy for cervical
cancer

• Dr Naveena Singh, Edit Titmuss,
• Dr JoAnne Chin Aleong, Geoffrey Curran,
• Dr Michael Sheaff, Mr Ian Jacobs,
• and Mr John Shepherd

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Cervical Cancer
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Cervical cancer -incidence(per 100,000 women)
Where reliable data is available the world wide
incidence of cervical cancer varies across
continents and from country to country. In the
United Kingdom the incidence is about 10 per
100,000.
World wide approx 470, 000 cases 230,000
deaths
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CIN3 - incidence(per 100,000 women)
In the UK the incidence of high-grade CIN peaks
in the age range 25-29.
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Cervical cancer - incidence(per 100,000 women)
Whereas the incidence of cervical cancer has a
peak at age range at 35-39 followed by a second
peak at 75-79 years - probably representing
unscreened or poorly screened women.
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Cervical cancer -incidence

• In 2000 2424 registered cases in UK
• About 10 per 100,000 women
• In 2002 927 deaths/year in UK
• 12th commonest cancer women in UK
• 2 of all female cancers
• 2nd COMMONEST MALIGNANCY IN WOMEN UNDER 35

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Cervical cancer stage 1
Outside pelvis Stage I (40) - confined to cervix
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Cervical cancer stage 2
Stage II (30) - beyond cervix, not to pelvic
side wall or lower 1/3 vagina
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Cervical cancer stage 3
Stage III (25) - to side wall, lower 1/3 vagina
or hydronephrosis
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Cervical cancer stage 4
Stage IV (5) - involving bladder/rectal mucosa
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Cervical cancer - lymph node metastasis
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Cervical cancer - treatment modalities

• Surgery
• LLETZ/Cone biopsy
• Radical Hysterectomy
• Exenteration
• Radiotherapy
• Chemoradiation

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Cervical cancer - treatment

• Radical hysterectomy, radiotherapy and
  chemoradiation are all radical modalities
• Majority of cancers detected in younger women are
  early stage
• ? too radical for early disease
• ? can fertility be conserved

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Radical hysterectomy
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Radical trachelectomy

• Dargent et al, 1994
• Cx parametrium upper vagina removed
• Pelvic lymphadenectomy
• Isthmic-vaginal anastomosis
• Isthmic cerclage

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Radical trachelectomy

• Indications
• Women under 40
• Cancers up to Stage Ib (IIa)
• Strong desire to maintain fertility
• Over 90 carried out at St Bartholomews Hospital
• 3 recurrences and 1 death
• 26 live births

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Radical trachelectomy -follow-up

• CYTOLOGY IS CRUCIAL IN FOLLOW-UP
• Isthmic-vaginal smears are taken using brush and
  spatula
• 3 monthly in first year
• 4 monthly in second year
• 6 monthly from 2-5 years
• annually thereafter till 10 years
• After 10 years, discharged and sent to NHSCSP
  call-recall programme

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Follow-up

• Follow-up for 10-99 months
• No of smears/case 1-12 (mean 4)
• Interval from surgery to follow-up 2-99 months

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Results

• 197 smears from 32 patients
• Aged 22-36
• Diagnosis - all stage 1B1
• Squamous cell carcinoma 23
• Adenocarcinoma 8
• Adenosquamous 1

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Squamous cells

• Sole component in 81 smears (41) from 18
  patients, 3-60 months post-operative
• 3 cases (10) contained only squamous cells in
  all smears
• 35 smears (18) were cytolytic appeared vaginal
• Reason believed to be
• High metaplasia
• Difficulty in obtaining smear /or tight os

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Keratinisation

• Small keratinised cells seen in 29 (15) of
  smears
• No accompanying features of viral infection
• Prominent keratinisation
• Large numbers parakeratotic cells
• Anucleate squamous cells

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Endocervical cells

• Typical endocervical cells seen in 48 (28) of
  smears
• Histology showed ½ cases with endocervical mucosa
  at upper end of trachelectomy specimen
• Generally well preserved
• Occasional reactive changes
• Multinucleation

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Endometrial cells

• Four types
• Functional endometrium
• Menstrual endometrium
• Lower uterine segment
• Tuboendometrial metaplasia

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Cytology Endometrial cells

• Present in 114 (58) of cases.
• Small cells with hyperchromatic nuclei
• Potential to overcall if not attentive to
• Low power arrangement
• Two cell population
• LMP date
• Nature of previous malignancy

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Lower uterine segment sampling

• LUS sampling feature of brush samples or due to
  shortening of canal after treatment
• Avoid misinterpretation as endometriosis or
  glandular malignancy
• Two cell types
• Cuboidal epithelial cells
• Tangles of stromal cells
• Epithelial microbiospies
• Tubular fragments endometrial glands
• Branching sheets
• 3D clusters
• Mitotic figures seen up to day 19

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Tubo endometrial metaplasia

• Begin histological change in the cervices women
  treated by cone biopsy or LLETZ for CIN or CGIN
• Avoid misinterpreting TEM for CIN or CGIN
• Response to injury
• Cells smaller than endocervical cells or squamous
  metaplasia
• Centrally or basally situated small round or oval
  nuclei
• Uniformly hyperchromatic with inconspicuous
  nucleoli
• Pseudo-stratification and nuclear crowding or
  super-crowding
• Finely granular evenly dispersed chromatin
• Inconspicuous nuclear membrane
• Some cells devoid cytoplasm, others with small
  rim
• 2D or 3D with 3D glandular structures with
  reversed rosettes (nuclei arranged around a clear
  central zone)
• May see terminal bars/cilia
• Mitotic figures rare cases
• Apoptotic figures and feathering not seen

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Stromal fragments

• 32/73 (44) within 12 months after surgery
• 33/127 (27) post-12 months
• Heterogeneous in nature
• Two types
• Plumper type of endometrial origin
• Elongated thin wavy nuclei in fragments including
  capillary vascular channels
• Not always possible to categorise

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Abnormal Cells
As the smears are from a specialist patient
population a high referral rate from screeners is
to be expected and any smear showing an
abnormality should be referred for consultant
level opinion
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Abnormalities

• One fifth slides referred for consultant level
  opinion
• 3 unsatisfactory
• 10 borderline
• 1 severe dyskaryosis
• 3 glandular abnormality
• 3 recurrent carcinoma

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Recurrences

• 3 patients developed recurrent disease
• 1 recurrent VAIN 1-2 with koilocytosis
• 2 with pelvic recurrences of squamous carcinoma
• Both detected in asymptomatic patients

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Recurrent squamous cell carcinoma
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Recurrent squamous cell carcinoma
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Recurrent squamous cell carcinoma
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Adequacy

• 81 (41) smears only squamous cells
• Do these represent inadequate sampling?
• High squamous metaplasia
• Difficulty in obtaining smear, tight os
• 10 cases never had glandular cells in any smear
• Recurrent case detected on proper isthmic smear

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Recommendations on adequacy

• Smears up to 24 months after trachelectomy must
  contain glandular cells
• If repeat smear is known to have been taken by
  proper method and is still devoid of glandular
  cells, report as negative but record absence of
  glandular cells

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False positives

• 4 (2) overcalled from 3 patients
• 3 severe dyskaryosis
• 1 glandular neoplasia
• Two reclassified as negative at MDT review
• 3rd patient underwent trucut biopsy before slide
  review

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Reporting recommendations

• Smears contain only squamous cells
• report as unsatisfactory if within 2 years of
  follow-up and negative thereafter
• Abnormal smears
• should be followed by smear review and MDT
  discussion to avoid unnecessary investigations

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Conclusion

• Recurrence can be detected cytologically before
  clinical/radiological presentation
• Unique in containing large numbers of endometrial
  cells
• Potential for over-diagnosis

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Summary

• Trachelectomy represents conservative surgical
  approach for early stage invasive cervical cancer
• Likely to increase in popularity
• Cytology is mainstay of follow-up
• Essentially cytological features are predictable
  and similar to those after cone biopsy

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