Differentiation of thymoma and thymic carcinoma from oesophageal carcinoma, lung carcinoma, other carcinomas and mesothelioma

Immunohistochemistry

CD5 positivity is charcteristic of type C thymomas, whereas types A and B, and most extra-thymic malignancies are negative for CD5. The initial study6 used antibodies Leu 1 and UCHT2 on crystat section:

 

 

CD5

 

typical thymoma

0/116

atypical thymoma

2/56

thymic carcinoma, squamous cell type

7/76

lung carcinoma

0/156

breast carcinoma

0/46

oesophageal carcinoma

0/66

gastric carcinoma

0/66

colonic carcinoma

0/96

cervical carcinoma

0/36

   

Subsequent studies have confirmed this finding, while also showing the value of CD99 to deomnstrate the immature lymphocytes typical of type B thymoma:

 

 

CD5

CD99+ lymphocytes

 

benign thymoma

0/177

15/157

invasive thymoma, NOS

0/217

15/157

Type B3 thymoma / well-differentiated thymic carcinoma

0/67

6/67

borderline B3/C thymic tumour

2/37

2/37

 Type C thymoma / thymic carcinoma

squamous cell carcinoma

9/97

0/97

basaloid carcinoma

1/17

0/17

clear cell carcinoma

1/17

0/17

mucoepidermoid carcinoma

0/17

 

lymphoepithelioma-like carcinoma

2/47

0/47

adenocarcinoma

0/17

 

undifferentiated carcinoma

2/27

0/27

carcinoma NOS

1/17

0/17

overall

16/207

0/187

thymic neuroendocrine tumours

thymic carcinoid

0/37

 

small cell carcinoma

0/47

0/17

thyroid spindle epithelial tumor with thymus-like differentiation (SETTLE)

0/17

 

non-thymic carcinomas metastatic to mediastinum (6 lung, 1 cervix, 1 thyroid, 1 prostate)

0/97

 

various extra-mediastinal carcinomas

0/317

 

melanoma

0/57

 

mesothelioma

0/37

 

       

CD72, a ligand of CD5, found on the surface of B-cells, is not expressed by thymomas or thymic carcinomas6.

 

Positivity for p63 with negativity for TTF-1, WT-1 and thrombomodulin appears to be helpful in differentiating both thymomas and thymic carcinomas from mesotheliomas (negative for p63 and TTF-1 but positive for WT-1 and thrombomodulin)and pulmonary adenocarcinomas (negative for p63, WT-1 and thrombomodulin but positive for TTF-1).

 

 

Thymoma

Thymic carcinoma

Mesothelioma

Pulmonary adenocarcinoma

 

Calretinin

1/351 ††

8/221 † ‡, 2/42

10/121 ‡‡

0/141

Mesothelin

0/351 †† ‡

8/221 † ‡

10/121 ‡

3/141

CK5/6

34/351 † ‡

21/221 ‡

9/121

9/141

Thrombomodulin

0/351 ††

0/221 ††

6/121 ‡

0/141

HBME-1

10/351

4/221 † ‡

7/121

8/141

WT-1

0/351 ††

1/221 ††

7/121 ‡

0/141

Ber-EP4

7/351 ‡‡

16/221 †

3/121 ‡‡

14/141

MOC-31

0/351 ‡‡

5/221 ‡‡

0/121 ‡‡

12/141

BG-8

4/351 ‡‡

16/221 ††

1/121 ‡‡

13/141

B72.3

4/351 ‡‡

3/221 ‡‡

0/121 ‡‡

10/141

CEA

0/351 ‡‡

5/221 ‡‡

0/121 ‡‡

12/141

CD15

10/351 ‡‡

17/221 ††

0/121 ‡‡

9/141

TTF-1

0/351 ‡‡

0/221 ‡‡

0/121 ‡

8/141

p63

35/351 †† ‡‡

22/221 †† ‡‡

0/121

0/141

CD5

0/351

9/221 † ‡‡

0/121

0/141

         
         
         
p values for difference in result from that for mesothelioma: ††; p<0.001, ; 0.001<p<0.05.
p values for difference in result from that for pulmonary adenocarcinoma: ‡‡; p<0.001, ; 0.001<p<0.05.

One additional finding is the potential usefulness of Ber-EP4, BG-8, and CD15 in the differential diagnosis between thymic carcinoma and predominantly epithelial thymoma (type B3), given the generally much lower frequencies of these markers in thymomas compared with thymic carcinomas, and particularly the nonreactiveness in type B3 thymoma1.

 

A small study has looked specifically at primary pleural thymomas in comparison with mesothelioma.

 

Another study concentrated on the differentiation from squamous and large cell carcinoma of the lung4.

 

 Results are for epithelial cells

Thymoma

Thymic carcinoma

Pulmonary large cell undifferentiated carcinoma

Pulmonary squamous cell carcinoma

 

CD5

1/14

3/6

1/10, focal

0/10

CD10

5/14

3/6

2/10, focal

6/10

CD1a

3/13 (2 nuclear)

2/6

2/10, nuclear

2/10, nuclear

CK7

8/14

6/6

8/10

8/10

TTF-1

0/14

0/6

3/10

0/10

         
         
         
         

13/14 thymomas contained a marked population of CD1a positive lymphocytes. It was concluded that CD1a positive lymphocytes may be helpful in identifying thymomas, CD5 positive epithelial cells in identifying thymic carcinomas and TTF-1 positivity helpful in identifying large cell pulmonary carcinomas.

 

CD70 may also be useful, staining the epithelial cells of thymic carcinomas but not thymomas or extrathymic carcinomas:

 

Thymoma, spindle cell

0/25

 

Thymoma, mixed cell

0/25

Thymoma, polygonal-oval cell

0/95

Atypical thymoma

1/55

Thymic carcinoma (squamous cell type)

7/85

Thymic carcinoid

0/15

pulmonary squamous cell carcinoma

0/75

pulmonary adenocarcinoma

0/55

pulmonary small cell carcinoma

0/35

pulmonary large cell carcinoma

0/25

oesophageal squamous cell carcinoma

0/45

oesophageal small cell carcinoma

0/15

mesothelioma

0/25

   

 

A further study used less generally available antibodies on frozen sections3:

 

 

UH-1

IL-1R

bek

 

thymoma

20/29

29/29

26/29

oesophageal carcinoma

0/12

3/12

4/12

pulmonary adenocarcinoma

0/12

0/12

0/12

pulmonary squamous cell carcinoma

0/9

8/9

7/9

       
       
       
       
       

 

References

1Pan, C. C., P. C. Chen, et al. (2003). "Expression of calretinin and other mesothelioma-related markers in thymic carcinoma and thymoma." Hum Pathol 34(11): 1155-62.

2Matsuno, Y., Morozumi, N., Hirohashi, S., Shimosato, Y., Rosai, J. Papillary carcinoma of the thymus: report of four cases of a new microscopic type of thymic carcinoma. Am J Surg Pathol 1998;22:873-80.

3Shiraishi, J., M. Utsuyama, et al. (2001). "Immunohistological analysis of thymoma by molecules differentially expressed in the thymic cortex and medulla, and its application in the differential diagnosis of thymoma from esophageal and lung cancer." Pathol Res Pract 197(9): 611-9.

4Pomplun, S., A. C. Wotherspoon, et al. (2002). "Immunohistochemical markers in the differentiation of thymic and pulmonary neoplasms." Histopathology 40(2): 152-8.

5Hishima, T., M. Fukayama, et al. (2000). "CD70 expression in thymic carcinoma." Am J Surg Pathol 24(5): 742-6.

6Hishima, T., M. Fukayama, et al. (1994). "CD5 expression in thymic carcinoma." Am J Pathol 145(2): 268-75.

7Dorfman, D. M., A. Shahsafaei, et al. (1997). "Thymic carcinomas, but not thymomas and carcinomas of other sites, show CD5 immunoreactivity." Am J Surg Pathol 21(8): 936-40.

This page last revised 30.3.2004.

©SMUHT/PW Bishop