Thymoma, types A and B

Types A and B thymomas are epithelial neoplasms showing thymus-like (organotypic) differentiation. The number of non-neoplastic lymphocytes is variable.

They may occur at any age, with a peak incidence at 55-65 years. Cases in the first two decades of life are extremely rare. There is an association of thymomas with the MEN1 syndrome.

Classification

Various histological classifications of thymoma have been proposed:

	WHO0	Muller-Hermelink	Kuo3
	Type A	Medullary	Spindle cell
	Type AB	Mixed	Small polygonal cell
			Mixed
	Type B1	Predominantly cortical	Organoid
	Type B2	Cortical	Large polygonal cell
	Type B3	Well-differentiated thymic carcinoma	Squamoid

Prevalences of subtypes^0,4

	Type A	5-10%
	Type AB	20-35%
	Type B1	5-10%
	Type B2	20-35%
	Type B3	10-25%
	Type C	10-25%
	Rare types	2.5%4

Correlation of type with stage⁷

Type	I	II	III	IVA	IVB	Invasive	subsequent recurrence	20 year survival
A	7		1			13%, 11%8	0% (0/8)	100%8
AB	27	15	1		1	39%, 42%8	2% (1/44)	87%
B1	15	5	4	1		40%, 47%8	9% (2/25)	91%
B2	11	10	12	2	1	69%, 69%8	19% (7/36)	59%8
B3	2	2	6			80%, 85%8	20% (2/10)	36%8
C		1	8		5	100%	-

Incidence of myasthenia gravis⁷

Type	Incidence of myasthenia gravis
A	0% (0/8)
AB	7% (3/44)
B1	40% (10/25)
B2	56% (20/36)
B3	10% (1/10)
C	0% (0/14%)

Cytogenetic abnormalities:

		chromosomal gains	chromosomal losses
	Type A		homogenous -6p6
	Type AB		-5q21-22, -6q, -12p, -16q
	Type B1
	Type B2		aberrations of multiple cormosomes6
	Type B3	+1q	aberrations of multiple cormosomes6, including -6, -13q
	Thymic squamous cell carcinoma	+1q, +17q, +18	aberrations of multiple cormosomes6, including -3p, -6, -13q, -16q, -17p,

• The various WHO-defined histological thymoma types, including the lymphocyte-rich AB and B2, exhibit different profiles of genetic aberrations⁶.

• Some of the lymphocyte-poor type B3 thymomas are genetically closely related to the lymphocyte-rich B2 thymomas and may arise from them by gain of genetic aberrations⁶.

• Only WHO type A thymomas exhibit a generally homogeneous profile of genetic abnormalities mainly involving chromosome 6, in contrast with the heterogeneity in the other thymoma types⁶. Loss of heterozygocity at 6q25 may be common to tumourogenesis across the spectrum of thymomas⁶.

• Metastatic behavior shows a significant correlation with allelic imbalances at 8p11.21 and 16q22.1⁶.

• Some type A and AB thymomas share apparently similar profiles of genetic aberrations with type B or C thymomas but maintain their distinctive morphology and benign clinical behavior⁶.

Immunohistochemistry

In type B thymomas, the T-lymphocytes are immature, as evidenced by their positivity for CD1a and CD99. Positivity for CD79a may also be common¹.

Steroid receptor positivity for oestrogen receptor ERa and progesterone receptor PR-B has been demonstrated in the epithelial cells of thymomas.

		cases positive	H score
	ERa	87/1322	86±802
	ERb	9/1322	7±92
	PR-A	5/1322	3±52
	PR-B	65/1322	56±682
	Androgen receptor	20/1322	14±122

There is a progressive reduction in immunoreactivity for both ERa and PR-B from Type A, through types AB, B1 and B2 to Type B3².

Survival

Histological type correlates with stage, but is also an independent predictor of survival for stage I and II tumours^4,8.

		5 years
	Type A	100%4
	Type AB	100%4
	Type B1	94%4
	Type B2	75%4
	Type B3	70%4
	Type C	48%4

Smaller studies have perhaps lacked the power to show differences in survival other than between thymoma (types A and B) and thymic carcinoma (type C)⁵.

References

¹ Hashimoto, M., Y. Yamashita, et al. (2002). "Immunohistochemical detection of CD79a expression in precursor T cell lymphoblastic lymphoma/leukaemias." J Pathol 197(3): 341-7.

² Ishibashi, H., T. Suzuki, et al. (2003). "Sex steroid hormone receptors in human thymoma." J Clin Endocrinol Metab 88(5): 2309-17.

³ Kuo, T. (2000). "Cytokeratin profiles of the thymus and thymomas: histogenetic correlations and proposal for a histological classification of thymomas." Histopathology 36(5): 403-14.

⁴ Chen G, Marx A, Wen-Hu C, et al. New WHO histologic classification predicts prognosis of thymic epithelial tumors: a clinicopathologic study of 200 thymoma cases from China. Cancer 2002; 95:420-9

⁵ Chalabreysse L, Roy P, Cordier JF, et al. Correlation of the WHO schema for the classification of thymic epithelial neoplasms with prognosis: a retrospective study of 90 tumors. Am J Surg Pathol 2002; 26:1605-11

⁶ Inoue M, Starostik P, Zettl A, et al. Correlating genetic aberrations with World Health Organization-defined histology and stage across the spectrum of thymomas. Cancer Res 2003; 63:3708-15 FULL TEXT

⁷ Okumura M, Miyoshi S, Fujii Y, et al. Clinical and functional significance of WHO classification on human thymic epithelial neoplasms: a study of 146 consecutive tumors. Am J Surg Pathol 2001; 25:103-10

⁸ Okumura M, Ohta M, Tateyama H, et al. The World Health Organization histologic classification system reflects the oncologic behavior of thymoma: a clinical study of 273 patients. Cancer 2002; 94:624-32

This page last revised 28.12.2004.

©SMUHT/PW Bishop