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 (9 type A, 10 type AB, 4 type B1, 7 type B2, 5 type B3¹)

Thymic carcinoma (4 keratinising squamous, 7 non-keratinising squamous, 8 lymphoepithelioma-like, 2 basaloid, 1 clear cell¹)

Mesothelioma

Pulmonary adenocarcinoma

Calretinin

1/35^{1 ††}

8/22^{1 † ‡}, 2/4 (papillary adenocarcinomas)²

10/12^{1 ‡‡}

0/14¹

Mesothelin

0/35^{1 †† ‡}

8/22^{1 † ‡}

10/12^{1 ‡}

3/14¹

CK5/6

34/35^{1 † ‡}

21/22^{1 ‡}

9/12¹

9/14¹

Thrombomodulin

0/35^{1 ††}

0/22^{1 ††}

6/12^{1 ‡}

0/14¹

HBME-1

10/35 (8 of the 10 positive cases were types A or AB)¹

4/22^{1 † ‡}

7/12¹

8/14¹

WT-1

0/35^{1 ††}

1/22^{1 ††}

7/12^{1 ‡}

0/14¹

Ber-EP4

7/35^{1 ‡‡}

16/22^{1 †}

3/12^{1 ‡‡}

14/14¹

MOC-31

0/35^{1 ‡‡}

5/22^{1 ‡‡}

0/12^{1 ‡‡}

12/14¹

BG-8

4/35^{1 ‡‡}

16/22^{1 ††}

1/12^{1 ‡‡}

13/14¹

B72.3

4/35^{1 ‡‡}

3/22^{1 ‡‡}

0/12^{1 ‡‡}

10/14¹

CEA

0/35^{1 ‡‡}

5/22^{1 ‡‡}

0/12^{1 ‡‡}

12/14¹

CD15

10/35^{1 ‡‡}

17/22^{1 ††}

0/12^{1 ‡‡}

9/14¹

TTF-1

0/35^{1 ‡‡}

0/22^{1 ‡‡}

0/12^{1 ‡}

8/14¹

p63

35/35^{1 †† ‡‡}

22/22^{1 †† ‡‡}

0/12¹

0/14¹

CD5

0/35¹

9/22^{1 † ‡‡}

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 (an in-house monoclonal antibody raised against thymic epithelial cells)

IL-1R

bek ( a kind of FGF receptor)

thymoma (2 type A, 2 type AB, 9 type B1, 9 type B2, 7 type B3)

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.

		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

		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
thymic neuroendocrine tumours	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

	Thymoma (9 type A, 10 type AB, 4 type B1, 7 type B2, 5 type B3¹)	Thymic carcinoma (4 keratinising squamous, 7 non-keratinising squamous, 8 lymphoepithelioma-like, 2 basaloid, 1 clear cell¹)	Mesothelioma	Pulmonary adenocarcinoma
Calretinin	1/35^{1 ††}	8/22^{1 † ‡}, 2/4 (papillary adenocarcinomas)²	10/12^{1 ‡‡}	0/14¹
Mesothelin	0/35^{1 †† ‡}	8/22^{1 † ‡}	10/12^{1 ‡}	3/14¹
CK5/6	34/35^{1 † ‡}	21/22^{1 ‡}	9/12¹	9/14¹
Thrombomodulin	0/35^{1 ††}	0/22^{1 ††}	6/12^{1 ‡}	0/14¹
HBME-1	10/35 (8 of the 10 positive cases were types A or AB)¹	4/22^{1 † ‡}	7/12¹	8/14¹
WT-1	0/35^{1 ††}	1/22^{1 ††}	7/12^{1 ‡}	0/14¹
Ber-EP4	7/35^{1 ‡‡}	16/22^{1 †}	3/12^{1 ‡‡}	14/14¹
MOC-31	0/35^{1 ‡‡}	5/22^{1 ‡‡}	0/12^{1 ‡‡}	12/14¹
BG-8	4/35^{1 ‡‡}	16/22^{1 ††}	1/12^{1 ‡‡}	13/14¹
B72.3	4/35^{1 ‡‡}	3/22^{1 ‡‡}	0/12^{1 ‡‡}	10/14¹
CEA	0/35^{1 ‡‡}	5/22^{1 ‡‡}	0/12^{1 ‡‡}	12/14¹
CD15	10/35^{1 ‡‡}	17/22^{1 ††}	0/12^{1 ‡‡}	9/14¹
TTF-1	0/35^{1 ‡‡}	0/22^{1 ‡‡}	0/12^{1 ‡}	8/14¹
p63	35/35^{1 †† ‡‡}	22/22^{1 †† ‡‡}	0/12¹	0/14¹
CD5	0/35¹	9/22^{1 † ‡‡}	0/12¹	0/14¹

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

	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

	UH-1 (an in-house monoclonal antibody raised against thymic epithelial cells)	IL-1R	bek ( a kind of FGF receptor)
thymoma (2 type A, 2 type AB, 9 type B1, 9 type B2, 7 type B3)	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