Before the advent
of immunohistochemistry , histochemical studies played an important role
in the diagnosis of mesothelioma.
produce the acid mucopolysaccharide, hyaluronic acid which can be
identified by staining with Alcian blue (pH 2.5) with and without
neutral mucin droplets within tumour cells or tubular lumina by periodic acid - Schiff reaction with diastase pretreatment strongly indicates that
the tumour is an adenocarcinoma and not mesothelioma.
Diagram showing pancytokeratin marker
strongly positive in mesothelioma
of mesothelioma is one based on exclusion.
There is no single immunohistochemical marker entirely specific for mesothelioma hence a
panel of antibodies are used to establish the diagnosis.
Immunohistochemistry is useful in the following areas:
differentiate between malignant epithelial mesothelioma and adenocarcinoma:
A combination of
monoclonal antibodies to carcinoembryonic antigen (CEA) , Leu-M1 ,
Ber-EP4, MOC31 or B72.3 can distinguish 90% pulmonary
adenocarcinomas from pleural mesothelioma.
In a recent publication, it
was suggested that immunostaining for cytokeratin 5/6 could assist
in distinguishing epithelial mesothelioma from lung adenocarcinoma.
antibodies are useful in identification of epithelial mesothelioma.
is extremely useful and is applicable to formalin fixed, paraffin embedded
differentiate between malignant epithelial mesothelioma versus reactive
antigen (EMA)- strong and diffuse positive membrane staining and/or Human
Milk Fat Globulin-2 (HMG2) favours mesothelioma over hyperplasia.
EMA may rarely show patchy
weak membrane staining of reactive mesothelium.
p53 protein is also highly
specific for mesothelioma over reactive mesothelial hyperplasia (this is
less specific than EMA).
Staining for cytokeratin
may be useful as it may help in the identification of invasion into deeper
3. To differentiate
between malignant sarcomatous mesothelioma from sarcoma, localized
fibrous tumour and reactive serosal fibrosis :
The pancytokeratin marker
AE1/AE3 and low molecular weight cytokeratin CAM5.2 are useful in the
diagnosis of mesothelioma.
Most sarcomas, reactive
serosal fibrosis and localized fibrous tumours are cytokeratin negative.
(Note: Epithelioid variant of sarcoma, synovial sarcoma and leiomyosarcoma may occasionally show
cytokeratin positivity ).
Vascular tumours: Mesotheliomas
do not express vascular markers (CD31, FactorVII ) .
It may not be
possible to differentiate epithelioid leiomyosarcoma from sarcomatoid
variant of mesothelioma as smooth muscle differentiation may be present in
the latter ( according to some authors these should be classified as
leiomyoid mesothelioma ).
Synovial sarcoma: These may be
confused with mixed and sarcomatoid variants of mesothelioma.
mucin or positive immunostaining for adenocarcinoma markers in
the epithelial elements are particularly useful.
Bcl-2 protein is
present in almost all cases of synovial sarcoma. It is rarely present in
differentiate malignant mesothelioma from lymphoma and thymoma:
lymphoma are high grade and are differentiated from mesothelioma by using
cytokeratin and lymphoid markers.
Thymoma arising in
pleura may be confused with solid and lymphohistiocytoid pattern of
mesothelioma. Immunohistochemistry is of little help in this area.
|Note : Among
positive mesothelioma markers, pancytokeratin, calretinin and
Tumor-1) are usually
recommended. It is known that virtually all mesothelioma are
positive for calretinin with nuclear and cytoplasmic staining, and
approximately 70% to 95% of mesotheliomas show nuclear positivity