PATHOHISTOLOGICAL DIAGNOSISAND DIFFERENTIAL DIAGNOSIS

Introduction

Malignant mesothelioma is a malignant tumour originating from mesothelial cells. Most frequently, it arises in the pleura (70–95%). Primary peritoneal mesothelioma is less frequent (6–10%). Rarely, the primary site of malignant mesothelioma is the pericardium or the tunica vaginalis of the testis [34]. The most frequent pleural and peritoneal tumour is metastatic carcinoma; therefore morphological diagnosis by the surgical pathologist has to take into account clinical history and radiology. Asbestos exposure is the highest risk factor ofpleural and peritoneal malignant mesothelioma and reported in approximately 54–90% of the patients. The mean latency period between exposure and tumour diagnosis ranges from 35 to  0 years. In peritoneal mesothelioma, an increased pulmonal asbestos exposure of the lung can be observed in 85% of the patients. Further, patients with peritoneal mesotheliomas have a higher pulmonal  asbestos exposure than those with pleural mesotheliomas. The incidence of malignant pleural  esothelioma shows marked variation in different countries. The highest incidence rates are reported from Great Britain, Belgium and Australia with annual incidences from about 30 cases per million.

In women, occupational asbestos exposure plays a minor role than in men. It has been found in approximately 23%. No occupational asbestos exposure has been found in young patients with malignant peritoneal mesothelioma. In women, malignant peritoneal mesothelioma occurs in younger age and is associated with better prognosis. Two percent to 5% arise in the first 2 decades of life. Other possible risk factors for malignant mesothelioma are radiation, recurrent peritonitis and simian virus 40 (SV 40). The association between Simian virus 40 (SV 40) and risk of mesothelioma development remains a controversial

discussion. Exposure to erionite (zeolith mineral fibre similar in appearance with amphibole asbestos) leads to higher incidences of mesothelioma and plays an important role in environmental exposure (Turkey). Prognosis is dependent on histological type. Longest survival can be seen in patients with epithelioid malignant mesothelioma. Patients with sarcomatoid malignant mesothelioma have the

worst prognosis and prognosis of biphasic malignant mesothelioma lies in between. Grading has not been proven to correlate with prognosis. For differential diagnosis between metastasis, primary malignant mesothelioma or reactive mesothelial proliferation, not only histology but also a panel of immunohistological markers is essential. 

Malignant Mesothelioma of the Pleura

The most common primary tumour of the pleura is diffuse malignant mesothelioma (WHO nomenclature), but often this tumour is designated as malignant mesothelioma or simply as mesothelioma 

Morphology

Macroscopy and Tumour Spread Early malignant mesothelioma begins as multiple nodules, usually in the parietal pleura and less frequently in the visceral pleura. Later, nodules become confluent and diffuse tumour

growth leads to pleural mass, pleural thickening (more than 1 cm to several cm) and effusion. Parietal and visceral pleura are both involved and cannot be separated. The tumour has a firm, sometimes gelatinous consistency, and spreads throughout the pleura, grows along interlobular spaces and encloses the lung. Hyaline pleural plaques are often present – up to 40% 

Histological Patterns

 Malignant mesothelioma has the capability to reveal either epithelial or mesenchymal differentiation or both. Depending on the histological growth pattern, epithelioid, sarcomatoid, biphasic and desmoplastic malignant mesothelioma are distinguished according to the WHOclassification

Epithelioid Mesothelioma

The most frequent one is epithelioid malignant mesothelioma. It shows different growth patterns,

mostly tubular or tubulopapillar. Tubules are small and papillary structures have vasculated stroma cores . Papillary areas may show psammoma bodies. Sheet-like or microglandular (also revered to as adenomatoid) growth pattern can also be seen and are admixed with tubulopapillar areas . Sometimes pseudo-signet ring cells are demonstrable (negative for mucine) or clear cell differentiation 

Sarcomatoid Mesothelioma

Sarcomatoid malignant mesothelioma shows spindle cells, which are arranged in a haphazard  pattern, or giant cells with anaplasia. Tumour growth resembles fibrosarcoma or malignant fibrous histiocytoma. Focal areas of osteosarcomatous or chondrosarcomatous differentiation can be found. In sarcomatoid malignant mesothelioma, greater atypia, mitotic activity and more necrosis can be found compared to epithelial mesothelioma

Biphasic Mesothelioma 

Biphasic malignant mesothelioma comprises both the aforementioned components, showing an epithelioid and sarcomatoid differentiation. At least 10% of the tumour should be represented by one of the components to be called biphasic. About 30% of all mesotheliomas are biphasic [23, 53], but the more tumour tissue sampled, the higher percentage of biphasic differentiation can be detected. Spindle cell differentiation of tumour cells must not be confused with pronounced stroma reaction in epithelioid

mesothelioma. Focal osseous differentiation is possible. 

Rare Forms of Mesothelioma

In desmoplastic malignant mesothelioma, dense eosinophilic stroma of desmoplastic type predominates throughout at least 50% of the tumour. Atypical spindle cells are distributed in a patternless manner. Particularly in small biopsies, desmoplastic malignant mesothelioma may be confused with reactive sclerosing pleuritis as there might not be overt infiltration of fat or muscle

tissue or sarcomatoid differentiation to prove malignancy. Desmoplastic mesothelioma can be regarded as a subtype of sarcomatoid malignant mesothelioma.

Differential Diagnosis of Malignant

Mesothelioma and Pleural Metastases

Although diffuse malignant mesothelioma is the most common primary neoplasm arising in the pleura, metastatic carcinoma by far is the most frequent pleural tumour overall [4, 32]. In daily routine pleural biopsy diagnostic, one has to deal with the question, if mesothelial proliferation is reactive or neoplastic, primary mesothelioma or metastatic. Histology is the gold standard of diagnostic, but morphology alone cannot solve

the problem and needs to be accomplished by additional immunohistochemical analyses

Morphological Differences

Epithelioid malignant mesothelioma needs to be distinguished from metastatic carcinoma, particularly of the lung, breast, gastrointestinal tract and prostate. To separate malignant mesothelioma from metastases, immunohistochemistry is essential, but some morphological characteristics narrow the possible differential diagnosis . Clear cell differentiation of mesothelioma can be misdiagnosed for metastatic renal cell

carcinoma, clear cell adenocarcinoma of the lung or malignant melanoma. Sarcomatoid malignant mesothelioma raises the possible differential diagnosis of spindle cell carcinoma, different types of sarcoma (leiomysarcoma, synovial sarcoma, angiosarcoma, pleomorphicsarcoma and others) and again sarcomatoid

renal cell carcinoma or malignant melanoma. Macroscopic appearance of the tumour is important, since malignant mesothelioma usually shows diffuse growth and metastases of the above-mentioned tumours are mainly circumscribed. Thymoma and solitary fibrous tumour, respectively, has to be taken into consideration as well. Reactive changes like sclerosing pleuritis or papillary mesothelial hyperplasia need to be ruled out Pleomorphic malignant mesothelioma can mimic pleural metastasis of pleomorphic carcinoma, mostly of the lung, or pleomorphic sarcoma (malignant fibrous histiocytoma). Psammoma bodies can be seen in metastasis of serous ovarian cancer, primary peritoneal carcinoma,

papillary lung or renal carcinoma as well as in papillary or tubulo-papillary malignant mesothelioma. They do not prove the metastatic origin of the tumour

Immunohistochemistry

Immunohistochemistry is essential for diagnosis of epithelioid malignant mesothelioma, for delineating reactive from neoplastic mesothelial proliferation and for excluding or ascertaining pleural metastases, mainly adenocarcinoma. With the exception of TTF-1, there is no other single immunohistochemical marker which is able to prove or exclude malignant mesothelioma, yet. A panel of different immunohistochemical markers

has to be applied 

Important Markers for Differential Diagnosis

Pancytokeratin

Epithelioid mesothelioma is strongly positive for pancytokeratin. More than 70% of sarcomatoid mesotheliomas are positive with the broad spectrum cytokeratin in the cytoplasm. 

CK 5/6

64–100% of epithelioid malignant mesotheliomas express CK5/6 [55, 56] and it also helps to highlight tumour cells in desmoplastic malignant mesothelioma. The marker serves to distinguish mesothelioma from lung adenocarcinomas. This marker usually characterises squamous cell differentiation but can also be found in adenocarcinoma of the lung in 2–19%

Calretinin

Calretinin is one of the best known and most specific positive mesothelioma markers. It is positive in almost all epithelioid mesotheliomas with a nuclear and cytoplasmatic staining pattern. Nevertheless, specificity is not 100%, because focal cytoplasmatic  expression can be found 0–38% of lung carcinomas, whereas positive nuclear otaining is only found in mesothelioma .

WT-1

WT-1 is negative in adenocarcinoma of the lung, and cells of malignant mesothelioma show positive reaction in 75–90% . In recent studies none of the lung adenocarcinomas were found to express WT-1 . It is one of the best markers to distinguish malignant mesothelioma from adenocarcinoma of the lung. Serous adenocarcinoma of the ovary also shows positive WT-1 reaction.

D2-40

Malignant mesothelioma shows membrane positivity of D2-40 (podoplanin) in more than 96% (Fig. 5.9), adenocarcinoma of the lung focally in up to 7% . D2-40 is a marker that stains a protein which is expressed in lymphatic endothelial cells . It can be a very useful marker in histological specimens to diagnose malignant mesothelioma  but not in serous effusion cytological smears, because it

does not distinguish mesothelioma cells from metastatic cells of serous adenocarcinoma, seminoma or malignant peripheral nerve sheath tumour, which are also positive 

TTF-1

To our knowledge, TTF-1 has never been proven to be expressed in malignant mesothelioma but is positive in about 85% of lung adenocarcinoma (nuclear expression), but not in squamous cell carcinoma. Reversely, it does not prove the pulmonary origin of pleural metastases because thyroid carcinoma is

also positive and some other primary tumours rarely show TTF-1 expression, one among them being adenocarcinoma of the colon in 10%

BerEP4

Adenocarcinoma of the lung is positive for BerEP4 (also known as HEA) in more than 5%. Malignant mesothelioma focally expresses BerEP4 in up to 20% [38, 55, 56]. Fifty-five percent to 90% of pulmonary adenocarcinomas are positive for CEA and malignant mesothelioma expresses this marker in less than 5%

MOC-31

MOC-31 is another useful immunohistochemical marker to separate malignant mesothelioma from pulmonary adenocarcinoma. This antibody reacts with most carcinomas and only patchily with epithelioid mesothelioma. It is positive in more than 95% of adenocarcinoma and in up to 10% of malignant mesothelioma

BG8

Analogous expression is achieved with BG8 [38, 55, 56], which shows diffuse strong positivity in 98–100% of adenocarcinoma. Only weak and focally staining in 3–7% of malignant mesothelioma have been described . BG 8 could be useful in differentiating epithelioid mesothelioma from lung adenocarcinoma

and serous carcinomas.

Claudin

Claudin 4 is a marker, which is expressed in pleural metastasis of adenocarcinoma of the lung, breast, gastrointestinal tract and ovary in 100% [29]. The majority of epithelioid and sarcomatoid malignant mesotheliomas are negative, but positivity may be found in a minority of cases 

Conclusions Immunohistochemistry

Immunohistochemical markers expressed in malignant epithelioid mesothelioma or in metastasis of adenocarcinoma (modified according to the International Consensus Statement of Pathologic Diagnosis of Malignant Mesothelioma . Sensitivity of the markers is 80% or more. At least two mesothelioma/ carcinoma markers should be applied the International Consensus Statement of Pathologic Diagnosis of Malignant Mesothelioma . Sensitivity of each marker should be at

least 80%. When there are discordant findings, additional markers should be performed. Positivity of calretinin, especially nuclear expression, and/or another of the mesothelioma markers in combination with expression of CK5/6 is very suggestive of malignant mesothelioma. Expression of CK5/6 together with negativemesothelioma markers and positive carcinoma  markers is found in metastasis of squamous cell

carcinoma and in a minority of adenocarcinoma or adenosquamous carcinoma of the lung 

Reactive Versus Neoplastic

Mesothelial Proliferation

In small, superficial pleural biopsies, differentiation between reactive or neoplastic mesothelial proliferations can be difficult. Macroscopic appearance in important and need to includes into the diagnosis [20] and has to take into account if the lesion is diffuse or circumscribed, inflammation, pneumonia of the lung, bilateralism, involvement of parietal or visceral pleura. Papillary mesothelial proliferation occurs in

reactive hyperplasia and malignant epithelioid mesothelioma. Cytological atypia can be more pronounced in reactive hyperplasia, whereas malignant mesothelioma cells usually are uniform and bland. Proliferation, for example, Ki67, in malignant mesothelioma is higher than in reactive changes . Fibrovascular cores in papillary lesions are a clue for malignancy; papillary proliferations in reactive

changes mainly consist of epithelial cells .

Reactive mesothelial proliferations tend to express desmin and are negative for EMA whereas neoplastic mesothelial cells show a contrarious pattern. It is very important, which EMA-clone is applied for immunohistochemistry: clone E29 should be

used and is positive in 75% of malignant mesothelioma and negative in reactive mesothelial proliferation. Clone Mc5 is not specific and positive in 70% of malignant mesothelioma and 60% of reactive changes

Primary Pleural Tumours Other than

Malignant Mesothelioma

Several other tumours arise in the pleura, benign and malignant. Adenomatoid tumour is a benign mesothelial tumour mostly seen in the tunica vaginalis of the genital tract but it can develop in the pleura also. It is a circumscribed, solitary tumour with epithelioid morphology, tubular structures and fibrous stroma. Pseudo-signet ring cells can be found and may be mistaken for metastasis of signet ring cell carcinoma.

Cytology usually is uniform. Well-differentiated papillary mesothelioma rarely develops in the pleura. It is mainly seenin the peritoneum and is described below. Synovial sarcoma is a biphasic tumour and is

very rarely seen in the pleura . Differential diagnosis is biphasic malignant mesothelioma. Most synovial sarcomas are pleural metastases and only a minority is primary to the pleura. Patients usually are younger than patients with malignant mesothelioma; the average age is 33 years . They are localised compared to the diffuse growth of malignant mesothelioma. Epithelioid component can be difficult to detect, tumour growth is more compact with long spindle cell fascicles compared to malignant mesothelioma, which tends to have smaller, less cellular fascicles with greater pleomorphism. It is important to know that synovial sarcoma can be positive for calretinin and malignant mesothelioma for CD99. Demonstration

of Syt-translocation t(X;18) provides the diagnosis 

Peritoneal Mesothelioma

Pathohistological Diagnosis

Malignant peritoneal mesothelioma is characterised by a peritoneal tumour mass with unspecific clinical symptoms like abdominal pain, abdominal swelling, anorexia, weight loss, and/ or ascites. Radiological features are non-specific. Therefore, the histological examination is essential to yield correct diagnosis. Examination of ascites or fine-needle aspiration can be useful but is of low diagnostic potential because of the small numbers of malignant cells in the fluid and their cytological resemblance to normal mesothelial

cells. The use of immunocytology can be useful in some cases. But in general, sampling of tumour biopsy has a higher diagnostic significance whereas immunohistochemical examination is indispensable in distinguishing MPM from other lesions and neoplasias. 

Macroscopy

Malignant peritoneal mesothelioma consists of multiple or innumerable nodules approximately 1.5 cm in diameter. The tumour mass is undistinguishable from peritoneal metastases or primary peritoneal carcinoma. The cut surface is frequently heterogeneous with solid regions and embedded cystic or mucoid areas into the tumour mass. The localised subtype forms a typically circumscribed

mass invading adjacent organs without a diffuse growth through the abdominal cavity. In contrast, the diffuse type shows a widespread expansion and involvement of the abdominal organs along parietal and visceral peritoneum. Infiltrating per continuitatem into the stomach from serosa to the mucosa is seen in every fourth case. Involvement of liver, abdominal wall, pancreas, bladder, retroperitoneum or diaphragm with invasion into the pleural cavity are less common. In 7% of the cases, abdominal, thoracic or inguinal lymph node metastases are found. Haematogenous metastases are seen in the liver,

lung, pleura, pericard, kidney, pancreas or in bones.

Microscopy

Analogue to pleural mesotheliomas, malignant peritoneal mesothelioma is divided into three different major histological types: epithelioid mesothelioma, sarcomatoid mesothelioma and the mixed or biphasic type. There are further rare subtypes like the undifferentiated type (poor differentiated) or lymphohistiocytoid and

desmoplastic mesothelioma (that belongs to the sarcomatoid subtype). The most common type of malignant peritoneal mesothelioma is the epithelioid subtype in more than 50%. In approximately 25% of MPM, a sarcomatoid component can be found, but pure sarcomatoid mesothelioma is very infrequent in the peritoneum and more commonly seen in the pleura.

In women, a deciduoid subtype has been described, that can be mistaken for an extensive ectopic decidual reaction. This subtype can be found in women during pregnancy as well as in women of advanced age. Patients with this subtype have a worse prognosis with a median survival rate of 7 months. Asbestos exposure can be found in 35–80% . 75% of malignant peritoneal mesotheliomas

are epithelioid mesotheliomas resembling normal mesothelial cells. They are composed of trabecular, papillary or tubulo-papillary formed tumour nests. Microglandular or signet-ring cell patterns are also found. The tumour cells invade submesothelial connective tissue, fatty tissue and muscle which help to distinguish malignant mesothelioma from reactive mesothelial hyperplasia.

Malignant Mesothelioma of Tunica Vaginalis Testis 

Malignant mesothelioma of tunica vaginalis testis is a rare  tumour that belongs to malignant peritoneal mesothelioma because during embryonal period, tunica vaginalis testis evolves from invagination of the abdominal peritoneal membrane and is covered by mesothelial cells. Less than 5% of malignant peritoneal mesotheliomas are localised primarily in the tunica vaginalis testis . Several studies evaluated that mesotheliomas of tunica vaginalis testis are asbestos related in case

of significant asbestos burden

 Well-Differentiated Papillary Mesothelioma

Well-differentiated papillary mesothelioma is a rare subtype of epithelioid mesothelioma with low malignant potential in contrast to malignant peritoneal mesothelioma. It occurs more frequently in the peritoneum than in the pleura and it is typically most common in young woman without asbestos exposure, but its relation

to asbestos exposure remains still unclear. One study group reported an occupationally asbestos exposure in 42% of all examined patients. Macroscopically, the tumour size ranges from 1 cm to more than 3 cm, but more than half of the cases of well-differentiated papillary mesotheliomas are smaller than 1 cm.

Furthermore, it can occur as solitary type or multifocal type. The latter shows more aggressive behaviour. In some cases, patients with initial well-differentiated papillary mesothelioma die from diffuse malignant mesothelioma during the course of disease

Prognosis and Predictive Factors

The diffuse type of malignant mesothelioma is a highly aggressive tumour, whereas no characteristic features were found to distinguish favourable or less favourable groups. Women have a better outcome but the reason still remains unclear [78]. Well-differentiated papillary mesothelioma is associated with better prognosis. Distinction between histological subtypes is an important predictive value because epithelioid

mesothelioma has a better prognosis than the sarcomatoid or biphasic subtype. Several studies investigated on the value of potential prognostic factors. Male gender, age <53 years, loss of weight, tumour volume, sarcomatoid or biphasic histological subtype, mitotic count and nuclear size were identified as

negative prognostic factors, but further studies are needed to evaluate these features 

5Pathohistological Diagnosis and Differential Diagnosis 

Differential Diagnosis

Several neoplastic and non-neoplastic processes1 have to be excluded due to the infrequent incidence of malignant peritoneal mesothelioma and certain histomorphological similarities to other benign lesions and malignancies whereas malignant peritoneal mesotheliomas remains still a differential diagnosis.

Non-neoplastic lesions include inflammatory processes like reactive mesothelial proliferations related to peritonitis, tuberculosis, sarcoidosis or foreign body reaction and adhesions that develop after surgical intervention. In women, endometriosis and endosalpingiosis or decidual knots formed during pregnancy

caused by decidual transformation of the serosal membrane can impress as tumourous process. Neoplastic lesions have to be distinguished from peritoneal metastases, primary peritoneal   carcinoma, lymphoma, sarcoma and benign lesions/tumours like benign multicystic mesothelioma, adenomatoid tumour, leiomyomatosis peritonealis disseminata and gliomatosis peritonei 

Benign Lesions

Benign Multicystic Peritoneal Mesothelioma Benign multicystic peritoneal mesothelioma arises in pelvic serosa and forms a mulitcystic tumour mass occurring predominantly in young and middle-aged women. In less than 20%, benign multicystic peritoneal mesothelioma can be found in males . In contrast to malignant peritoneal mesothelioma, asbestos exposure is not found. The tumour comprises a multicystic tumour mass that is either solitary or in most cases diffuse or multilocated. The tumour cysts are translucent, filled with serous fluid and confluent and delimited by a fibrous band. The cysts measures less than 1 cm up to 20 cm in diameter. The multicystic mesothelioma has a benign or indolent course and is inclined to recur in one-half of the cases between 1 and 27 years. In rare cases, multiple recurrence and malignant transformation to malignant mesotheliomas have been observed 

Adenomatoid Tumour

Adenomatoid tumour – also designated as benign mesothelioma – is a very rare benign mesothelial tumour that forms gland-like tumour nests with adenoid, angiomatous or cystic structures with smooth muscle proliferations embedded in a fibromatous stroma. It occurs most frequently in the tunica vaginalis testis. Macroscopically, the Malignant Lesions

Peritoneal Metastases

Peitoneal metastases are secondary tumours of the peritoneum and the most common tumours of the peritoneum. Ovarian carcinoma, colorectal cancer and gastric cancer just as carcinomas of the pancreas, gallbladder, uterus and lung are the most frequent tumours that show peritoneal involvement. Peritoneal metastases represent advanced tumour stage and are associated with a poor prognosis. In patients with  olorectal carcinoma, peritoneal metastases occur in 10–15%. Primary ovarian carcinomas show peritoneal metastases in 65–70%, pancreatic carcinomas in 35% and gastric cancer in 25–30%. Peritoneal metastases

caused by separation of individual tumor cells from the primary tumour. The invasion of these dissociated tumour cells depends on the location of the primary tumour. Invasion in blood and lymphatic vessel is characteristic for carcinomas of the gastrointestinal tract. Tumours that are adherent to the peritoneum, like ovarian carcinomas, show direct peritoneal involvement. Frequently, peritoneal metastases show

similar histological pattern like their primary tumour; most of peritoneal metastases are adenocarcinomas. Tumour heterogeneity, like differences of tumour grading, causes diagnostic problems. Peritoneal metastases of a primary low-grade adenocarcinoma can show a highgrade pattern, for example. Loss of original

histological pattern can occur in tumours after chemotherapy. In such cases, clinical informations about pretreatment or knowledge of primary tumour site is helpful to confirm the correct diagnosis. Particularly, in case of mixed carcinomas like adenocarcinoma with partial endocrine type or adenosquamous carcinoma,

peritoneal metastases can consist of only one of the histological pattern. A correct diagnosis on the basis of conventional histology is difficultin most cases and additional immunohistochemistry is required.

Carcinoma of Unknown Primary (CUP)

Carcinoma of unknown primary (CUP) is seen in 3–5% of all tumour diseases. In 5–10% the peritoneum is involved (Muir 1995). On the other hand, 2–4% of primary peritoneal tumours represent the origin of CUP . Histologically, most peritoneal metastases are adenocarcinomas in 40–60%, undifferentiated carcinomas in 15–30%, squamous carcinomas in 15–20% and in 3–5% small cell carcinomas or endocrine

tumours are observed. Therefore, immunohistochemistry is necessary to classify tumour infiltration but in some cases the assignment to the localisation of the primary tumour site is not possible

Primary Peritoneal Carcinoma

Primary peritoneal carcinoma (PPC) is an extraovarian neoplasia that resembles surface epithelial tumours of ovarian origin. It occurs xclusively in middle-aged women between 53 and 62 years. Fifteen percent of ‘typical ovarian cancers’ are primary peritoneal carcinomas. It consists of confluent tumour masses

transforming omentum and mesenteriums to tumour bulks and involving the surface of the liver, anterior abdominal wall and the peritoneal side of the diaphragm. The most common histological subtype is serous adenocarcinoma whereas, like in surface carcinoma of the ovary, transitional cell, clear cell, mucinous or squamous cell carcinomas have been reported. Histologically and immunohistologically, PPC is undistinguishable from ovarian carcinoma. To separate these two tumour entities, certain criteria have

been developed

Primary Peritoneal Borderline Tumour

Primary peritoneal borderline tumour is a rare neoplasia of the peritoneum that only arises in women mostly between 16 and 67years of age. Median age is 32 years. Characteristically, this tumour shows morphological similarities to serous borderline tumour of the ovary but arises from the peritoneum without or with minimal involvement of the ovarian surface . Macroscopically, the tumour nodules appear

like non-invasive implants of ovarian borderline tumour with smaller knots or adhesions. Only in rare cases, tumour mass is found. Like ovarian borderline tumour, most tumours are of serous types with psammoma bodies

Immunohistochemistry

Malignant peritoneal mesothelioma shows the same immunohistochemical staining pattern like the pleural counterpart expressing calretinin, WT1 (Wilm’s tumour antigen 1), EMA, Cytokeratin 5/6, D2-40. Characteristically, they are negative for CEA, TTF-1, BerEp-4 (HEA), B72.3, MOC- 31, BG8 and Claudin-4 . A marker panel including antibodies that are frequently positive in mesotheliomas should be used. EMA and desmin help to distinguish benign mesothelial lesions from MPM in most cases.

Up to 80% of malignant mesotheliomas show positive immunostaining of EMA and up to 85% of benign mesothelial lesions express desmin. But both, EMA and desmin, have a low sensitivity and specificity of 70–75% differentiating benign from malignant mesothelial lesions, because weak membrane positivity of

EMA can be found in reactive mesothelial proliferation. On the other hand, some cases of malignant mesothelioma are EMA negative. To separate mesotheliomas from sarcomas, lymphomas or melanomas, the use of cytokeratin is helpful. 

Primary Peritoneal Carcinoma/Metastases

of Serous Ovarian Cancer Versus Malignant

Peritoneal Mesothelioma

Epithelioid type of malignant peritoneal mesothelioma shows close overlapping histomorphological similarities to primary peritoneal carcinoma/metastases of serous ovarian cancer; therefore, distinction of these tumour entities is very important for further therapy, because MPM is a radio- and chemotherapy-resistant malignancy with poor prognosis. Several studies evaluated expression of immunohistochemical markers

to differentiate malignant mesotheliomas from primary peritoneal carcinoma/metastases of serous ovarian carcinoma. A high sensitivity of h-Caldesmon, Calretinin and D2-40 as well as a high specificity of calretinin and D2-40 (95%) has been reported in mesotheliomas. In primary peritoneal carcinomas/metastases of serous ovarian carcinoma, estrogen receptor and BerEp4 show a high sensitivity, and non-mesothelioma markers (like estrogen receptor, progesterone receptor, B72.3, CA19-9, CD15 and to a lesser extent

BerEp-4) are characterised by a high specificity . In case of D2-40, some studies reported a limited use because D2-40 is expressed in 13–65% of primary peritoneal carcinomas/metastases of serous ovarian carcinoma. Estrogen receptor, BerEp-4, MOC-31 and BG8 are expressed in primary peritoneal carcinomas/metastases of serous ovarian carcinoma to a high extent but are negative or infrequently detectable in malignant mesotheliomas . In general, to differentiate malignant peritoneal

mesothelioma from primary peritoneal carcinomas/ metastases of serous ovarian carcinoma, a panel including antibodies that are frequently positive in mesotheliomas (like Calretinin and WT-1) on the one hand and non-mesothelial markers (like estrogene receptor, BerEP-4, MOC-1 and BG8) on the other hand should be used