Reactive mesothelium versus malignant
mesothelioma
This differential
may be extremely difficult, especially on small biopsies.
Immunohistochemistry
|
reactive
mesothelium |
malignant
mesothelioma |
comment |
Desmin |
83%(
8/10staining
generally strong and diffuse2, 8/103, 34/40(In
26 cases, desmin stained more than 75% of cells with high intensity,
in 5 cases ~50% of cells with moderate intensity and in 3 cases
less than 25% of cells with low intensity. Exfoliated reactive
mesothelial cells stained.)21) |
28%
( 10/45biphasic:
10/19, epithelioid 0/13, sarcomatoid; 0/131,
9/16epithelioid;
8/13, biphasic; 1/3. Staining was only focal.2, 4/3827
predominantly epithelioid, 4 predominantly spindle, 7 biphasic.
Desmin positive in epithelioid component in 4/38 and in spindle
cell component in 12/383
), 18/40(12/26
epithelioid, 4/10 sarcomatoid, 2/4 biphasic)16,
21/43(14/34
epithelioid, 5/7 sarcomatoid, 0/1 mixed and 1/1 lymphohistiocytoid
mesotheliomas)17,
6/60(all
60 cases were of epithelioid type. In all six cases, staining
was cytoplasmic. In two cases, more than 75% of cells stained
intensely: in four cases staining was less than 25% of cells and
of low intensity. Exfoliated malignant mesothelial cells were
negative.)21 |
Appears
to be useful. Examine epithelial component:
desmin is less useful in distinguishing reactive from neoplastic
spindle cell mesothelial proliferations |
EMA |
15%
(3/734, 5/205, 2/126
6/117, 8/40(8 cases showed moderate
staining of less than 25% of cells.)21) |
75%
(103/1414, 30/31diffuse linear membrane,
stronger in epithelioid areas5,
10/126, 76/1127, 48/60(staining
was strong and membranous. In 39 cases, more than 75% of cells
stained. In 9 cases less than 25% of cells stained but the staining
was strong.)21) |
Appears
to be useful. |
p53 |
9%
(0/208, 0/209, 0/4010,
0/1311, 0/2012, 0/136,
13/20(occasional
nuclei positive)5,
9/117), 1/7(This was a study of
the differentiation of desmoplastic mesothelioma from fibrous
pleurisy: the difference in staining for p53 was not significant.)20,
0/4021 |
59%
(14/208, 21/47epithelioid; 10/16,
biphasic; 9/19, sarcomatoid; 2/12. Some small biopsies shows very
intense staining.9,
9/3610, 19/4011, 30/3512,
5/126, 30/315, 78/1127),
8/15(This
was a study of the differentiation of desmoplastic mesothelioma
from fibrous pleurisy: the difference in staining for p53 was
not significant.)20, 27/60(In
only 2 cases did more than 75% of mesothelial cells show nuclear
staining. In 20 cases, less than 25% of cells were positive.)21 |
May
be useful. |
bcl-2 |
0/4413, 0/205,
0/1521 |
5/6213, 0/315,
0/1521 |
Does
not appear to be useful |
p-glycoprotein, p170 |
3%
(0/3514, 2/117, 0/1521) |
45%
(31/3314, 37/1067, 2/1521) |
Background
staining may make interpretation difficult |
PDGF
receptor b |
13%
(0/3515, 2/117, 6/15(Two
cases showed strong staining of more than 75% of cells, two cases
showed moderate staining of 26-75% of cells and two cases showed
low intensity staining of less than 25% of cells.)21) |
38%
(15/3315, 31/1127, 15/15(9
cases showed strong staining of more than 75% of cells; 6 cases
showed strong staining of 26-75% of cells)21) |
Probably
not useful |
Telomerase reverse
transcriptase |
0/318 |
67/6818 |
Needs the study
of more cases of reactive proliferation |
GLUT-1 |
0/4026 |
48/48(36/36
epithelioid, 11/11 biphasic, 1/1 sarcomatoid)26 |
|
| |
Sensitivities
and
specificities have been calculated in a review paper19:
|
p53 |
EMA |
bcl-2 |
p170 |
desmin |
number of studies |
105,6,7,8,9,10,11,12,20 |
54,5,6,7,21 |
35,13,21 |
37,14,21 |
32,3,21 |
staining in mesothelioma |
positive |
positive |
positive |
positive |
negative |
Sensitivity for mesothelioma |
epithelioid |
61% of
236 cases |
77% of
296 cases |
3% of
76 cases |
58% of
100 cases |
81% of
73 cases |
biphasic |
41% of
34 cases |
73% of
26 cases |
4% of
22 cases |
56% of
16 cases |
2
of 3 cases |
sarcomatoid |
54% of
39 cases |
25% of
20 cases |
10% of
10 cases |
17% of
18 cases |
|
not classified |
59% of
32 cases |
83% of
12 cases |
|
|
89% of
38 cases |
overall |
58%
of 341 cases |
74%
of 354 cases |
4%
of 108 cases |
52%
of 134 cases |
83%
of 114 cases |
staining in benign pleural disease |
negative |
negative |
negative |
negative |
positive |
Specificity for mesothelioma |
91%
of 218 cases |
89%
of 167 cases |
100%
of 93 cases |
97%
of 61 cases |
83%
of 60 cases |
| |
|
|
|
|
|
|
Proliferation markers MCM2
and Ki67 may be helpful22:
| |
Reference 22 |
MCM2 |
Ki67 |
|
|
Median |
Interquartile range |
Median |
Interquartile range |
Reactive mesothelial hyperplasia
(n=18) |
0.225 |
0.150-0.250 |
0.100 |
0.030-0.130 |
Reactive pleural fibrosis (n=15) |
0.230 |
0.110-0.380 |
0.170 |
0.055-0.285 |
Epithelioid mesothelioma (n=14) |
|
0.330 |
0.205-0.465 |
0.150 |
0.085-0.250 |
|
0.320 |
0.320-0.530 |
0.200 |
0.200-0.265 |
Sarcomatoid mesothelioma (n=10) |
non-hot spot |
0.265 |
0.225-0.360 |
0.215 |
0.165-0.280 |
hot spot |
0.525 |
0.410-0.595 |
0.285 |
0.200-0.440 |
| |
|
|
|
|
|
A MCM2 labelling index >0.32 identifies epithelioid malignant mesothelioma
with 100% specificity and 87.% sensitivity (14/16 cases) in the distinction
from reactive mesothelial proliferation. .
AgNORs have been studied but are
difficult to assess in paraffin sections.
| |
|
Mesothelioma |
Benign pleural disease |
|
n |
AgNOR count |
n |
AgNOR count |
Ayres23 |
epithelioid |
10 |
5.4 |
10 |
1.75 |
biphasic |
5 |
4.9 |
sarcomatoid |
5 |
7.5 |
undifferentiated |
5 |
5.0 |
Bethwaite24 |
10 |
5.1 |
11 |
3.7 |
Soosay25 |
7 |
3.7 |
9 |
1.9 |
Wolanski4 |
80 |
6.1 |
26 |
5.0 |
| |
|
|
|
|
|
See also the use of immunohistochemistry
in effusion cytology.
In situ hybridisation
against p16 is a promising method of differentiating malignant mesothelioma
from reactive mesothelium.
Fibrous pleurisy may show spaces mimicking fat
("fake fat") surrounded by cytokeratin-positive spindle cells,
a source of confusion with desmoplastic mesothelioma. These spaces
may be differentiated from true fat by their negativity for S-100 and
vimentin but weak positivity of luminal substance for Alcian Blue27.
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Hurlimann,
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4 Wolanski,
K. D., Whitaker, D., Shilkin, K. B., Henderson, D. W. The use of epithelial
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This page last
revised 7.3.2012.
©SMUHT/PW
Bishop