Differentiation of peritoneal mesothelioma and serous carcinoma

The differentiation of peritoneal epithelioid mesothelioma from serous papillary carcinoma of the ovary or peritoneum can be problematic. Most studies of the immunohistochemical differentiation of mesothelioma from adenocarcinoma have concentrated on pulmonary adenocarcinomas. However, several of the markers that are of proven utility in this context are less informative in the differentiation from serous carcinoma.

 

 

Papillary serous carcinoma

Peritoneal epithelioid mesothelioma

 

 

Calretinin

1/161, 4/452, 0/233, 5/134, 8/265, 14/456

3/31, 35/352, 28/323, 40/406

The positivity of some serous carcinomas makes this marker less than specific.

CK5/6

11/452, 5/233, 11/327, 9/265, 14/456

35/352, 17/323, 37/406

This marker is of limited value in this context.

Thrombomodulin

7/208, 1/452, 6/233, 2/456

6/188, 26/352, 18/323, 29/406

Results vary between studies.

D2-40

6/456, 98/16916

37/406

The evidence from these two studies is conflicting..

Podoplanin

6/45 6

37/40 6

The specificity for mesothelioma is higher than that of calretinin but the sensitivity is lower.

BerEP4

25/309, 45/452, 3/610, 20/233, 45/456

4/352, 3/323, 5/406

Strong staining is a useful marker for serous carcinomas

B72.3

47/4711, 33/4612, 37/4413, 13/2014, 10/1015, 27/309, 39/452, 33/456

0/2812, 3/1014, 0/2015, 0/352, 0/406

This marker has specificity for serous carcinomas but limited sensitivity.

CD15

34/4612, 32/4413, 6/2014, 8/1015, 17/309, 28/452, 7/233, 26/456

3/2812, 0/414, 3/2015, 0/352, 2/323, 0/406

This marker has specificity for serous carcinomas but low sensitivity.

MOC-31

44/452, 44/456

1/352, 2/406

This marker may be very helpful in this context, with a higher specificity than Ber-EP4.

 

 

BG-8

33/456

1/406

 

CD44H

5/233

15/323

No value

Ca19-9

31/452,

30/456

0/352, 0/406

This marker has specificity for serous carcinomas but low sensitivity.

Ca-125

42/452, 21/233

33/35, 8/323

Limited value

pCEA

7/452, 2/233

3/323

No value

mCEA

1/233

0/323

No value

HBME-1

40/452

31/352

No value

PLAP

11/452

0/352

 No value

44-3A6

28/452

16/352

 No value

S-100

14/452

0/352

 No value

Vimentin

15/452

9/352

 No value

EMA

45/452

35/352

 

       

The optimum panel is probably BerEP4 and MOC-31 with calretinin, and either D2-40 or podoplanin3,6.

 

Ultrastructure

 

 

Serous papillary carcinoma

Epithelioid mesothelioma

 

Microvilli

Straight microvilli of variable length, less prolific than in mesotheliomas and confined to the apical surface. Cell membranes are closely apposed. Intracytoplasmic lumina are absent.

Long slender branching microvilli. They may be confined to the apical surface, may also be present on the basal surface or may cover the entire cell membrane. Cells are separated by gaps that often contain microvilli. Microvilli may also be found on intracytoplasmic lumina.

Cytoplasm

 Bundles of intermediate fibres are rare.

The cytoplasm contains numerous intermediate filaments arranged in bundles.

Ciliated cells

Multi-ciliated cells may occur

Rare

     

 

.

References

1 Doglioni, C., Tos, A. P., Laurino, L., Iuzzolino, P., Chiarelli, C., Celio, M. R., Viale, G. Calretinin: a novel immunocytochemical marker for mesothelioma. Am J Surg Pathol1996;20:1037-46.

2 Ordonez NG. Role of immunohistochemistry in distinguishing epithelial peritoneal mesotheliomas from peritoneal and ovarian serous carcinomas. Am J Surg Pathol 1998; 22:1203-14

3 Attanoos RL, Webb R, Dojcinov SD, et al. Value of mesothelial and epithelial antibodies in distinguishing diffuse peritoneal mesothelioma in females from serous papillary carcinoma of the ovary and peritoneum. Histopathology 2002; 40:237-44

4 Cathro HP,Stoler MH. The utility of calretinin, inhibin, and WT1 immunohistochemical staining in the differential diagnosis of ovarian tumors. Hum Pathol 2005; 36:195-201

5 Chu AY, Litzky LA, Pasha TL, et al. Utility of D2-40, a novel mesothelial marker, in the diagnosis of malignant mesothelioma. Mod Pathol 2005; 18:105-10

6 Ordonez NG. The diagnostic utility of immunohistochemistry and electron microscopy in distinguishing between peritoneal mesotheliomas and serous carcinomas: a comparative study. Mod Pathol 2006; 19:34-48

7 Reis-Filho JS, Simpson PT, Martins A, et al. Distribution of p63, cytokeratins 5/6 and cytokeratin 14 in 51 normal and 400 neoplastic human tissue samples using TARP-4 multi-tumor tissue microarray. Virchows Arch 2003; 443:122-32

8 Attanoos RL, Appleton MAC, Goddard H et al. Thronmbomodulin expression in malignant peritoneal mesothelioma and serous papillary adenocarcinoma of the ovary. J Pathol 1995;176:S49A.

9 Rothacker D,Mobius G. Varieties of serous surface papillary carcinoma of the peritoneum in northern Germany: a thirty-year autopsy study. Int J Gynecol Pathol 1995; 14:310-8

10 Cherchi PL, Marras V, Capobianco G, et al. Immunohistochemical evaluation of a new epithelial antigen, Ber-EP4, in ovarian cancer: preliminary results. Eur J Gynaecol Oncol 2001; 22:433-5

11 Thor A, Gorstein F, Ohuchi N, et al. Tumor-associated glycoprotein (TAG-72) in ovarian carcinomas defined by monoclonal antibody B72.3. J Natl Cancer Inst 1986; 76:995-1006

12 Bollinger DJ, Wick MR, Dehner LP, et al. Peritoneal malignant mesothelioma versus serous papillary adenocarcinoma. A histochemical and immunohistochemical comparison. Am J Surg Pathol 1989; 13:659-70

13 Wick MR, Mills SE, Dehner LP, et al. Serous papillary carcinomas arising from the peritoneum and ovaries. A clinicopathologic and immunohistochemical comparison. Int J Gynecol Pathol 1989; 8:179-88

14 Khoury N, Raju U, Crissman JD, et al. A comparative immunohistochemical study of peritoneal and ovarian serous tumors, and mesotheliomas. Hum Pathol 1990; 21:811-9

15 Wick MR, Mills SE,Swanson PE. Expression of "myelomonocytic" antigens in mesotheliomas and adenocarcinomas involving the serosal surfaces. Am J Clin Pathol 1990; 94:18-26

16 Bassarova AV, Nesland JM,Davidson B. D2-40 is Not a Specific Marker for Cells of Mesothelial Origin in Serous Effusions. Am J Surg Pathol 2006; 30:878-82

This page last revised 24.7.2006.

©SMUHT/PW Bishop