Gynaecological Pathology

Reporting
Cervical Pathology
Dr Raji Ganesan
Birmingham
 Format
• Introduction
• Cervical biopsy
• Difficulties in diagnosis of CIN
• p16
• Cervical loop
• Squamous carcinoma – diagnosing and
staging
• Hysterectomy for squamous carcinoma
• Glandular neoplasia
• Delegate questions
Surgical pathology
reporting
• Purpose: diagnosis of disease so that the
clinician can make a management decision
• Emphasis: On bottom line diagnosis
• Pressure: On time but accuracy is critical
• Reports generally created by a single
pathologist hence little time for reflection or
peer review
• Importance of clear, concise, unambiguous
reports
Reporting cervical pathology
– the punch biopsy
• What are the diagnoses that
affect clinical management?
- CIN3, CGIN, SMILE, invasion
- Diagnosis of CIN2
- If a diagnosis of CIN2 is made
the patient may be offered
ablative treatment.
- If a diagnosis of CIN2+ is made
the patient is likely to be offered
excisional treatment.
CIN2 – a difficult
diagnosis!
15 laboratories across New Mexico
Nearly 40000 biopsies
Categorised as
CIN1 to include CIN1, HPV, koilocytosis
CIN2 to include CIN1 -2, CIN2
CIN2 – 3 to include CIN2 – 3 and HSIL
not specified
CIN3

Cytology and age taken into account

p16 use not assessed

CIN2 varied from 7.2 to 22.3% (one outlier at 1.5%)

Use of p16 in non invasive
cervical pathology
• p16
recommended to
differentiate
between CIN 2/3
and immature
squamous
metaplasia/atroph
y/reparative
changes
Use of p16 in non invasive
cervical pathology
• To clarify a diagnosis of
CIN2
• Block positive favours
high grade CIN
• Non block or negative
staining favours low
grade or non-HPV
associated pathology
What if p16 does not correlate with my
morphological impression?
What if p16 positive, HPV test
negative?
Initial biopsy p16 LEEP diagnosis
diffuse block p16 CIN2 and CIN3 (HSIL)
positive (28 - 66.7%)
negative p16 (7 - 16.7%) Benign or CIN1

focal/patchy p16 (7 - CIN2 – 4 (HSIL)

16.7%) CIN1 - 3
Other situations where I
have found p16 useful

• Diagnosis of CTZ
• Unexpected CIN
• Tubo-endometrioid metaplasia
• Ciliated CGIN
Reporting cervical
pathology – the biopsy
• How many levels?
- 3 levels recommended by the tissue pathway
document.
- If there is little squamous epithelium, disrupted
surface, cross-cutting, non correlation, I would
do an additional 3 levels
• When p16?
- p16 recommended to differentiate between CIN
2/3 and immature squamous
metaplasia/atrophy/reparative changes
The cervical biopsy

• When do I call a biopsy inadequate?

- rare
- when there is no transformation zone sampling,
unless specifically mentioned as directed biopsy
- when the sample if disrupted or crushed or very
small
- when there is no glandular tissue in context of
cytology diagnosis of glandular dysk
The cervical biopsy

• When do I call a friend?

- regular multiheaders –
discrepancy with cytology,
previous biopsy or
colposcopy
- a diagnosis of CIN2
- interpretation of p16
Reporting cervical
pathology - the loop
• Trimming a loop
• Painting
• Turning over the end block
• Multiple slices in one block
• More than one piece - don't fret. Identify the
epithelial surface and cut parallels
• Top hat - don't fret - identify convexo
concave surface.
 Understanding the
margins
Endocervical margin
Endocervical
margin clearance Deep radial margin
(less than10mm)
Ectocervical margin
was significantly
correlated with
recurrence in
stage 1A cervical
cancers

Raspagliesi F et
al
Int J Gynecol
Cancer. 2005
Jan-Feb;15(1):88-
93.
Ectocervical margin Ectocervical margin
Ectocervical margin
 Ink the resection margins
Slice serially perpendicular
Don’t put
to os
epithelial
surface on
bench

Slices 2.5 to
3mm apart

One slice per

cassette

Slicing the loop or cone biopsy

Crescendo – decrescendo slice pattern
Thanks to Dr Lynn Hirschowitz
 Reporting cervical
pathology – the loop
• The variations:
- Loop in multiple pieces – identify the epithelial
surface
- Top hat – try and identify the concavo-convex
surface
• Levels:
- One deep level to see ‘full face’ of slice
- Levels to see margin involvement or routine
levels in all cases to rule out invasion – no role
Kenwright D, Braam G, Maharaj D, Langdana F. Multiple levels on LLETZ biopsies do not contribute to patient
management. Pathology. 2012 Jan;44(1):7-10
 Cervical pathology
reporting – the loop
• What matters clinically?
- Whether there is invasion or not.
- What is the stage? Unifocal vs multifocal?
• For audit and governance
- Grade of CIN
- Correlation with cytology or previous biopsy and/or colposcopy findings
• For audit and governance
- Grade of CIN
- Correlation with cytology or previous biopsy and/or colposcopy findings
• Features suggesting that there may be invasion
- Involvement of crypts by expansile CIN3 and luminal necrosis
- Large volume of CIN3

al-Nafussi A, Hughes D. J Clin Pathol 1994; 47: 799 – 804.

Ostor A..Int J Gynecol Pathol 1993; 12: 193 – 207.
Tidbury P, Singer A, Jenkins D. Br J Obstet Gynaecol 1992; 99: 583 – 6.
• Hypermaturation and
eosinophilia of basal
epithelial cells
• Loss of basement
membrane
• Loss of basal palisade
• Angulated buds
• Stromal reaction
Measuring invasion - depth

Measure from the base of the epithelium (surface or glandular)

from which the carcinoma arises. If there is no obvious
epithelial origin measure from the tumour base (deepest focus
of tumour invasion) to the base of the nearest surface
epithelium.
 Measuring invasion - width

The maximum horizontal

dimension/width of tumour is
measured in the section in which
the width is greatest (from the edge
at which invasion is first seen, to
the most distant edge at which
invasion is identified).
The ‘third’ dimension
Staging – do not use the term
microinvasive – means different
things to different groups
• FIGO does not include the term ‘microinvasive’
carcinoma
• Term ‘microinvasive’
- in UK = FIGO stage IA1 +/- IA2 disease
- in USA = stage IA1 disease
• American SGO defines tumours with LVI and dimensions
of FIGO stage IA tumours = FIGO stage IB
• RCPath dataset has discouraged the term
‘microinvasive carcinoma’ and for using the specific
FIGO stage as a descriptor
FIGO Stage allocation

• Multifocal vs unifocal carcinomas

• RCPath guidance
• ICCR guidance
• Evidence
Evidence
• 208 cases of squamous carcinoma on LLETZ
or cone
• 104 stages as FIGO 1A1
• 26 – more than one focus of invasion (4 not
included)
• 21/22 – repeat LLETZ or cone due to margin
involvement by CIN or carcinoma – none (9 to
91 month follow up) has had abnormal cytology
or tumour recurrence
• 11/21 could have been classed as 1B1
• Recommended – if greater than 2mm between
foci - multifocal
Other guidance
regarding measurements
• At trachelectomy or hysterectomy final
measurements should include the previous
specimens
• Maximum depth = greatest depth in the
specimens
• Maximum horizontal dimension = add
together the horizontal dimensions – maybe
an overestimate.
Reporting cervical
pathology – the
hysterectomy
• Trimming – guidance RCPath and ICCR
• Special consideration – the hysterectomy
after multiple loops, hysterectomy after
chemoradiotherapy, the paracervical tissue.
• Important to record – depth of invasion of
cervical stroma (inner, middle or outer third),
lvsi – both predict recurrence but do not
affect survival.
 The presacral space (PSS) is at the top.
rectum (R) and the pararectal spaces
(PRS).
The rectovaginal space (RVS)
vagina (V).
vesicovaginal space (VVS).
bladder (B) anteriorly
paravesical space (PVS).
Between the pararectal space and
the paravesical space is the lateral extent
of the cardinal ligament,
originally described as the "web" by
Wertheim.
The web contains the venous network
of the internal iliac vein.
Anterior to the bladder
is the space of Retzius (SR), the
retropubic space.

https://www.youtube.com/watch?v=fEjYfm2TXhs
 Delegate questions
• Should we treat ‘cannot exclude stage 1B1’ cervical
cancers, for very small tumours, but seen in 3-4
consecutive slices, more conservatively than ‘proper
1B1’ tumours (clearly >7mm across on glass slides)?
• The clinicians are aware of this and hopefully the new
BGCS guidelines and the SHAPE trial will address this
issue
• WRT - ‘cannot exclude stage 1B1’ – I find this
unhelpful. I strongly recommend the use of available
guidelines, consistence within your clinical group,
clearly explain the reasoning behind your staging in
your report and at MDT. Sometimes I might state ‘final
staging after MDT discussion’
 Delegate questions
• I sometimes find it difficult to definitively
identify the endocervical margin in a LLETZ
specimen. What tips do you have for this?
 Delegate questions
• and why is an involved endocervical margin treated
differently to an involved ectocervical margin?
• I am assuming that the involvement is by CIN or CGIN.
Irrespective of whether it goes to the margin, CIN is
followed up by TOC.
• CGIN is followed up by TOC only when completely
excised.
• Follow up of Stage 1A1 – if CIN goes to the margins and
carcinoma completely excised – re-excise
• Follow up completely excised Stage 1A1 – cytology at 6,
12 and annual x 9 years – return to normal
• Follow up completely excised Stage 1A2 and
conservatively treated 1B1 – management by gynae onc.
Delegate questions
• Reporting of cervical punch biopsies. On the
proforma there is a heading ‘Extension into crypts’ I
struggle with this as sometimes the epithelium
seem thick and may extend into crypts but as a
crypt is not seen clearly the distinction is hard to
make. So my question is when is there extension
into crypts on a cervical punch biopsy and what are
the criteria for it?
• Not aware of proforma for biopsies. Extension into
crypts is an item on loop reporting proforma.
Reason explained earlier.
Delegate questions
• LLETZ specimens and CIN extending to margins. How
much should we chase margin status? Should we turn end
blocks over?
• Not my practice. If the trimming is consistent (audit )
then usually not a problem
• How close is too close?
• CIN to margin not measured routinely
• What matters clinically?
• With CIN – excised or not excised
• My impression is that cases with early stage cancer get a
repeat LLETZ if the CIN is not excised. Otherwise, it's
usually a 'test of cure' only at next follow up.
• Yes
Delegate questions

• Creeping CGIN: What is its definition and

differential diagnosis?
• Not a term that I recognise but could be used
if CGIN is extending beyond the cervix
Delegate questions
• In intestinal type cervical adenocarcinoma, do
you see floating mitoses and/or apoptotic
bodies just like in usual type of cervical
adenocarcinoma and if you see them, does it
mean almost certainly primary cervical rather
than met from colo-rectum?
• Very rare but significant differential diagnosis.
Usually metastasis from colorectal primary will
show dirty necrosis. ‘Clean’ apoptosis
commoner with cervical primary. Immunos very
distinctive and useful