Reactive mesothelium versus malignant mesothelioma

This differential may be extremely difficult, especially on small biopsies.

Immunohistochemistry

 

reactive mesothelium

malignant mesothelioma

comment

Desmin

83%( 8/102, 8/103, 34/4021)

28% ( 10/451, 9/162, 4/383 ), 18/4016, 21/4317, 6/6021

Appears to be useful. Examine epithelial component

EMA

15% (3/734, 5/205, 2/126 6/117, 8/4021)

75% (103/1414, 30/315, 10/126, 76/1127, 48/6021)

Appears to be useful.

p53

9% (0/208, 0/209, 0/4010, 0/1311, 0/2012, 0/136, 13/205, 9/117), 1/720, 0/4021

59% (14/208, 21/479, 9/3610, 19/4011, 30/3512, 5/126, 30/315, 78/1127), 8/1520, 27/6021

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, 6/1521)

38% (15/3315, 31/1127, 15/1521)

Probably not useful

Telomerase reverse transcriptase

0/318

67/6818

Needs the study of more cases of reactive proliferation

GLUT-1

0/4026

48/4826

 
 

 

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

 

Labelling indices

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)

non-hot spot

0.330

0.205-0.465

0.150

0.085-0.250

hot spot

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.

 

References

1 Mayall, F. G., Goddard, H., Gibbs, A. R. Intermediate filament expression in mesotheliomas: leiomyoid mesotheliomas are not uncommon. Histopathology 1992;21:453-7.

2 Hurlimann, J. Desmin and neural marker expression in mesothelial cells and mesotheliomas. Hum Pathol 1994;25:753-7.

3 Scoones DJ, Richman PI. Expression of desmin and smooth muscle actin in mesothelial hyperplasia and mesothelioma. J Pathol 1993;169SL188A (abstract).

4 Wolanski, K. D., Whitaker, D., Shilkin, K. B., Henderson, D. W. The use of epithelial membrane antigen and silver-stained nucleolar organizer regions testing in the differential diagnosis of mesothelioma from benign reactive mesothelioses. Cancer 1998;82:583-90.

5 Cury, P. M., Butcher, D. N., Corrin, B., Nicholson, A. G. The use of histological and immunohistochemical markers to distinguish pleural malignant mesothelioma and in situ mesothelioma from reactive mesothelial hyperplasia and reactive pleural fibrosis. J Pathol 1999;189:251-7.

6 Casalots J, Tarroch X, Forcada P et al. Utility of epithelial membrane antigen and p53 in the differential diagnosis of benign reactive processes from malingnacy in pleural biopsy specimens. Virchows Archives 1999;435:286 (abstract).

7 Roberts, F., Harper, C. M., Downie, I., Burnett, R. A. Immunohistochemical analysis still has a limited role in the diagnosis of malignant mesothelioma. A study of thirteen antibodies. Am J Clin Pathol 2001;116:253-62.

8 Kafiri, G., Thomas, D. M., Shepherd, N. A., Krausz, T., Lane, D. P., Hall, P. A. p53 expression is common in malignant mesothelioma. Histopathology 1992;21:331-4.

9 Mayall, F. G., Goddard, H., Gibbs, A. R. p53 immunostaining in the distinction between benign and malignant mesothelial proliferations using formalin-fixed paraffin sections. J Pathol 1992;168:377-81.

10 Ramael, M., Lemmens, G., Eerdekens, C., Buysse, C., Deblier, I., Jacobs, W., van Marck, E. Immunoreactivity for p53 protein in malignant mesothelioma and non- neoplastic mesothelium. J Pathol 1992;168:371-5.

11 Cagle, P.T., Brown, R.W. and Lebovitz, R.M. p53 immunostaining in the differentiation of reactive processes from malignancy in pleural biopsy specimens. Hum Pathol 1994;25:443-8.

12 Esposito, V., Baldi, A., De Luca, A., Claudio, P.P., Signoriello, G., Bolognese, A., Centonze, P., Giordano, G.G., Caputi, M., Baldi, F. and Giordano, A. p53 immunostaining in differential diagnosis of pleural mesothelial proliferations. Anticancer Res 1997;17:733-6.

13 Segers, K., Ramael, M., Singh, S.K., Weyler, J., Van Meerbeeck, J., Vermeire, P. and Van Marck, E. Immunoreactivity for bcl-2 protein in malignant mesothelioma and non- neoplastic mesothelium. Virchows Arch 1994;424:631-4.

14 Ramael, M., van den Bossche, J., Buysse, C., van Meerbeeck, J., Segers, K., Vermeire, P. and van Marck, E. Immunoreactivity for P-170 glycoprotein in malignant mesothelioma and in non-neoplastic mesothelium of the pleura using the murine monoclonal antibody JSB-1. J Pathol 1992;167:5-8.

15 Ramael, M., Buysse, C., van den Bossche, J., Segers, K. and van Marck, E. Immunoreactivity for the beta chain of the platelet-derived growth factor receptor in malignant mesothelioma and non-neoplastic mesothelium. J Pathol 1992;167:1-4.

16 Garcia-Prats, M. D., C. Ballestin, et al. (1998). "A comparative evaluation of immunohistochemical markers for the differential diagnosis of malignant pleural tumours." Histopathology 32(5): 462-72.

17 Gonzalez-Lois, C., Ballestin, C., Sotelo, M. T., Lopez-Rios, F., Garcia-Prats, M. D., Villena, V. Combined use of novel epithelial (MOC-31) and mesothelial (HBME-1) immunohistochemical markers for optimal first line diagnostic distinction between mesothelioma and metastatic carcinoma in pleura. Histopathology 2001;38:528-34.

18 Kumaki, F., Kawai, T., Churg, A., Galateau-Salle, F. B., Hasleton, P., Henderson, D., Roggli, V., Travis, W. D., Cagle, P. T., Ferrans, V. J. Expression of Telomerase Reverse Transcriptase (TERT) in Malignant Mesotheliomas. Am J Surg Pathol 2002; 26:365-370

19 King J, Thatcher N, Pickering C, et al. Sensitivity and specificity of immunohistochemical antibodies used to distinguish between benign and malignant pleural disease: a systematic review of published reports. Histopathology 2006; 49:561-8

20 Mangano WE, Cagle PT, Churg A, et al. The diagnosis of desmoplastic malignant mesothelioma and its distinction from fibrous pleurisy: a histologic and immunohistochemical analysis of 31 cases including p53 immunostaining. Am J Clin Pathol 1998; 110:191-9

21 Attanoos RL, Griffin A,Gibbs AR. The use of immunohistochemistry in distinguishing reactive from neoplastic mesothelium. A novel use for desmin and comparative evaluation with epithelial membrane antigen, p53, platelet-derived growth factor-receptor, P-glycoprotein and Bcl-2. Histopathology 2003; 43:231-8

22 Sington JD, Morris LS, Nicholson AG, et al. Assessment of cell cycle state may facilitate the histopathological diagnosis of malignant mesothelioma. Histopathology 2003; 42:498-502

23 Ayres JG, Crocker JG,Skilbeck NQ. Differentiation of malignant from normal and reactive mesothelial cells by the argyrophil technique for nucleolar organiser region associated proteins. Thorax 1988; 43:366-70

24 Bethwaite PB, Delahunt B, Holloway LJ, et al. Comparison of silver-staining nucleolar organizer region (AgNOR) counts and proliferating cell nuclear antigen (PCNA) expression in reactive mesothelial hyperplasia and malignant mesothelioma. Pathology 1995; 27:1-4

25 Soosay GN, Griffiths M, Papadaki L, et al. The differential diagnosis of epithelial-type mesothelioma from adenocarcinoma and reactive mesothelial proliferation. J Pathol 1991; 163:299-305

26 Kato Y, Tsuta K, Seki K, et al. Immunohistochemical detection of GLUT-1 can discriminate between reactive mesothelium and malignant mesothelioma. Mod Pathol 2007; 20:215-20

27 Churg A, Cagle P, Colby TV, Corson JM, Gibbs AR, Hammar S, et al. The fake fat phenomenon in organizing pleuritis: a source of confusion with desmoplastic malignant mesotheliomas. Am J Surg Pathol. 2011 Dec;35(12):1823-9.

This page last revised 7.3.2012.

©SMUHT/PW Bishop