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 demonstrate 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
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

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 , 2/4(papillary adenocarcinomas)2	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( a kind of FGF receptor)
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.