April 2014
Dr J King
Dr K Syred
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90% mesotheliomas are linked to asbestos
exposure
May be eligible for compensation
3 yr survival rate 8%
Subtype related to prognosis and different
treatment options
◦ Epithelioid 1yr survival 52%
◦ Sarcomatoid 1 yr survival 13%
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Correlation of tissue diagnosis with clinical
and radiology
IHC:
◦ Panel 1: TTF-1, CEA, calretinin, CK5, D240, WT-1,
MOC31
◦ Panel 2: MNF116, CD15, CK7, CK20
Ihc
Reactive
Malignant
-/+
+ Strong
membranous
Desmin
+
-
p53
-
+
EMA
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Identify practice within our department
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Typing
Assess what ihc has been performed
Determine any improvements in diagnosis
Report quality
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Reviewed mesothelioma reports in the last 9
months (1/1/14 – 30/9/14)
Identify further work done
Possibly devise an improved panel of markers
make diagnosis more efficient and cost
saving
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‘6.4 Pathological
Histological type should be stated (epithelioid,
biphasic, sarcomatoid (desmoplastic variant if
present). Given the need for ancillary investigations
to make the diagnosis, the immunohistochemistry
panel used should be documented, this being at
least two ‘mesothelium-associated’ markers and
two ‘epithelium-associated’ markers for epithelioid
and biphasic tumours (discussed in section 5). For
sarcomatoid variants, due to the wide differential
diagnosis, the full repertoire of antibodies used
should be listed.’
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‘For pleural mesothelioma-like tumours with
an epithelial component, it is recommended
that immunolabelling for both calretinin and
TTF-1 is routinely carried out.’
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‘As with biopsies, cytological findings should be correlated
with the clinical and imaging findings to establish whether
the available cytological material is sufficient to render a
specific diagnosis or a clinically relevant differential
diagnosis. If a pleural cytology specimen is positive or
suspicious for malignancy, and there is no other specimen,
then material should undergo the same ancillary
investigations as for biopsies in terms of the differential
diagnosis, which ideally is via a cell pellet for histology as
this allows preservation of residual material. Identification
of an epithelial phenotype will allow a definitive diagnosis
of metastatic carcinoma. Identification of a mesothelial
phenotype will allow further management decisions in
terms of a definitive diagnosis of mesothelioma or further
sampling, dependent on the clinical scenario’
1.
2.
3.
4.
All diagnoses of mesothelioma should be typed.
Where immunohistochemistry is performed, there
should be a panel including 2 mesothelial and 2
epithelial markers.
If an epithelioid subtype, caltretinin and TTF-1
should be performed
Immunohistochemistry should be performed on
tissue rather than pleural fluid when available.
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Search on i-lab
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M-90503
M-90513
M-90523
M-90533
–
–
–
–
mesothelioma, NOS
fibrous mesothelioma, NOS
epithelioid mesothelioma, NOS
biphasic mesothelioma, NOS
1/1/14 – 30/9/14
From the list each report looked up on i-lab
Data in-putted into spread sheet
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Lab no
What procedure was done to obtain a diagnosis
Any previous relevant investigations
Any immunohistochemistry performed on the procedure
and if so what was ordered (the SPLI function was used
to identify the immunohistochemical stains performed
as not all of them were mentioned in the report. Where
mentioned in the report, the result (positive or negative)
was recorded).
It was noted if there was pleural fluid taken at the same
time as any biopsy.
If there was mention of a pleural fluid on the biopsy
form
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Diagnosis of mesothelioma if pleural or
peritoneal in during the time period stated
above.
Previous results e.g. any previous pleural
fluids sampled in previous years were also
included in this audit.
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Outside cases for review at the MDT eg. from
Truro.
Cases that are coded incorrectly.
LN biopsy for metastatic malignant
mesothelioma
PM histology as not all of the PMs would have
been picked
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Total 31 biopsies performed
◦ 3 excluded
1outside case
2 adenocarcinomas coded incorrectly
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Remaining 28
◦ 26 pleural bx - 20 had cytology at the same time
◦ 2 omental bx
◦ 27 had ihc
 1 did not as it was being performed on the fluid
◦ 1 had ihc on both bx and fluid
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Accompanying cytology
◦ 8/20 (36%) malignant or suspicious of malignancy
◦ 12/20 no malignant cells seen
◦ 6 cytology forms mentioned bx taken
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7 cases bx only taken
◦ 1 recurrent case with prev diagnosis 3 yrs ago
◦ 1 had 2 previous pleural fluids – blood only and
nmcs
◦ 5 did not have any previous procedure
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2 cases diagnosed on pleural fluid alone
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24/28 (86%) mesotheliomas diagnosed on
tissue were subtyped.
Type
No
Epithelioid malignancy
2
Epithelioid malignant mesothelioma
17
Epithelioid and sarcomatous malignant
mesothelioma
1
Biphasic malignant mesothelioma
3
Malignant mesothelioma
3
Recurrent malignant mesothelioma
1
Sarcomatoid malignant mesothelioma
1
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13/29 cytology cases were suspicious/
malignant.
only 7 were classed as mesothelioma and only
2 were subtyped. 2/13 = 15%
Report
No
Favour malignancy / malignancy strongly suspected 4
Atypical epithelioid cells highly suspicious of
malignancy
1
Malignant
1
Favour / suggestive / suspicious of mesothelioma
4
Mesothelioma
1
Epithelioid meosthelioma
2
biopsy
27
Accompanying cytology
2
Cytology alone
2
Previous cytology
4
Total
35
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39 different immuno-stains were ordered
Total of 286 ihc orders
Average = 8 per case
Mucin stains = 10
0
ABDPAS
DPAS
s100
CD34
CD31
Hepar 1
PSA
ER
CDX 2
CK20
TTF-1
p63
thrombomod…
pankeratin
Cam5.2
CEA
desmin
BerEp4
100
MOC31
p53
D240
CK7
WT-1
calretinin
MNF116
EMA
CK5
vimentin
CK19
Ae1/3
% number of ihc and special stains positive in malignant
mesothelioma
90
80
70
60
50
40
30
20
10
vimentin
CK19
Ae1/3
CK5
EMA
MNF116
calretinin
WT-1
CK7
D240
p53
MOC31
BerEp4
desmin
CEA
ABDPAS
DPAS
s100
CD34
CD31
Hepar 1
PSA
ER
CDX 2
CK20
TTF-1
p63
thrombomodulin
pankeratin
Cam5.2
% number of ihc and special stains negative in malignant
mesothelioma
100
90
80
70
60
50
40
30
20
10
0
Meso vs
adeno
panels
Ihc
Total
Pos bx
Pos cytol Neg bx
Neg
cytol
Panel 1
TTF-1
24
0
0
19
4
CEA
18
1
0
14
3
MOC-31 24
5
3
12
3
Calretini
n
33
20
7
3
0
CK5
26
19
5
1
0
D240
7
3
1
3
0
WT1
26
18
2
3
0
CKMNF1
16
12
10
0
1
0
CD15
0
0
0
0
0
CK7
9
5
1
2
0
CK20
8
0
0
5
1
Panel 2
Mesothelial markers
% positive
CK5
96%
(27/28)
Calretinin
90%
(29/32)
WT-1
88%
(22/25)
Epithelial markers
% positive
CEA
6%
(1/18)
BerEp4
29%
(7/24)
MOC31
35%
(8/23)
TTF1
0%
(0/23)
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30/35 (86%) had 2 epithelial and 2 meso
markers
Remaining 5:
◦ One had reactive panel
◦ 4 had both an epithelial and mesothelial marker,
some with 2 of one but not 2 of both
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23 of mesotheliomas typed as epithelioid
15/23 (65%) had both calretinin and TTF-1
performed
One had reactive panel
The remaining did not have TTF-1
2 were omental bx and may not need TTF-1
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Ihc performed on 27 of the biopsies
1 did not have ihc as it was requested on the
cytology (commented on in the report)
Only 1 patient had ihc on both biopsy and
cytology
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Standard 1: 86% tissue and 15% cytology
subtyped
Standard 2: 86% had 2 mesothelial and 2
epithelial markers
Standard 3: 65% epithelioid mesotheliomas
had calretinin and TTF-1
Standard 4: 1 had ihc on fluid rather than bx
and 1 had ihc on both
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New mesothelioma IHC panel
◦ CK5
◦ Calretinin
◦ WT-1
CEA
BerEp4
Moc31
TTF-1
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Proforma to guide reporting biopsies and
cytology
◦ Subtype
◦ List of ihc
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http://www.hscic.gov.uk/media/15038/Meso
theliomaaudit/pdf/EMBARGOEDTO120914_NLCA_Mes
o_Report_final.pdf
Standards and datasets for reporting cancers.
The dataset for the histological reporting of
mesothelioma. RCPath guidelines