Type A thymoma

Definition

An organotypic tumour composed of bland spindle or oval cells. Lymphocytes are sparse or absent. It is thought to be derived from thymic medullary epithelial cells, as evidenced by positivity for CD20, PE-35 and metallothionein.

Synonyms

Spindle cell thymoma, medullary thymoma.

Epidemiology

This type is relatively uncommon, accounting for 4% to19% of all thymomas1. Mean age at presentation is about 60 years. Cases in children have been reported1.

Clinical features

25% of type A thymomas are associated with myasthenia gravis. There may be pure red cell aplasia4.

Macroscopic appearances

Type A thymomas are usually Masaoka stage I2. They are well circumscribed and encapsulated but with only vague lobulation. They may be cystic.

Histopathology

These tumours are encapsulated, although there may be invasion through the capsule and, rarely, infiltration of the lung. Distinct lobulation and dissecting fibrous bands are absent.

The tumour cells are spindle or oval, the latter sometimes predominating. Nuclei are bland with dispersed to coarse chromatin and inconspicuous nucleoli. The spindle cells may be short and arranged in a haemangiopericytomatous pattern; alternatively, they may be long, resembling fibroblasts and taking on an interlacing or storiform pattern4. They may form glandular structures, rosettes (without a central lumen) or glomeruloid bodies, often immediately beneath the tumour capsule. There may be papillary projections into cystic spaces or meningioma-like whorls. Reticulin surrounds individual tumour cells. Few vessels are present. Vessels may form a haemangiopericytomatous pattern. Mitoses are rare. Formation of Hassall corpuscles is rare. Palisading around perivascular spaces is NOT a feature2. Infarction may occur.

There are few, or no, lymphocytes, except where there are foci of spindle cell micronodules in a lymphoid stroma. In particular, immature T-cells are lacking.

Rare spindle cell thymomas show nuclear hyperchromasia, pleomorphism and necrosis. It is not clear whether these are poorly differentiated cases of type A thymoma, spindle cell variants of type B3 thymoma or spindle cell type C thymoma / thymic carcinomas2. Rarely, there is transformation to thymic carcinoma: a focus of transformation may show necrosis.

Immunohistochemistry

	Epithelial cells
	AE1	positive0,1,6
	AE3	negative0,1,6
	CK20	negative0,1
	CD5	negative0,1
	CD20	focally positive0,2, 8/21(short spindle cell variant)4, 7/10(long spindle cell variant)4
	bcl-2	negative or only focally positive0,1
	CD57	variable/focal0,1, 80% of cases
	EMA	negative or only focally positive0,1
	metallothionein	positive0,1
	PE-35	positive (long spindle cells may be negative) 0,3
	laminin	surrounds individual cells0,1
	type IV collagen	surrounds individual cells0,1
	UH-1	0/2
	ERa	H score = 111±105
	PR-B	H score = 86±165
	p53	negative or low expression0,1
	Ki-67	negative or low expression0,1

	Lymphocytes (if present)
	CD3	positive0,1,4
	CD5	positive0,1
	CD1a	minority of T-cells0,1,2, majority of T-cells4
	CD99	minority of T-cells0,1,2
	CD20	negative, except in micronodular areas with a lymphoid stroma0,1

Cytogenetics

t(15;22)(p11;q11) and deletions of chromosome 6p have been reported0,1. There is loss of heterozygocity at 6q23.3-25.3, a feature shared with type B3 thymomas and squamous cell thymic carcinomas0.

Differential diagnosis

mesenchymal neoplasms

Management

Surgical removal, if complete, is almost always curative.

Prognosis

Type A thymomas do not recur if fully excised. The prognosis is excellent: 100% survival at 10 years. Even advanced tumours may show slow progression1. Exceptional cases of distant metastases or malignant transformation to thymic carcinoma have occurred.

References

0 Tumours of the Lung, Pleura, Thymus and Heart. WHO Classification of Tumours. IARC Press 2004.

1 J Rosai et al. Histological typing of tumours of the thymus. WHO International histological classification of tumours. Springer-Verlag, second edition, 1999.

2 Muller-Hermelink, H. K. and A. Marx (1999). "Pathological aspects of malignant and benign thymic disorders." Ann Med 31 Suppl 2: 5-14.

3 Hattori, H., H. Tateyama, et al. (2000). "PE-35-related antigen expression and CD1a-positive lymphocytes in thymoma subtypes based on Muller-Hermelink classification.An immunohistochemical study using catalyzed signal amplification." Virchows Arch 436(1): 20-7.

4 Pan, C. C., W. Y. Chen, et al. (2001). "Spindle cell and mixed spindle/lymphocytic thymomas: an integrated clinicopathologic and immunohistochemical study of 81 cases." Am J Surg Pathol 25(1): 111-20.

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

6 Nonaka D, Henley JD, Chiriboga L, et al. Diagnostic utility of thymic epithelial markers CD205 (DEC205) and Foxn1 in thymic epithelial neoplasms. Am J Surg Pathol 2007; 31:1038-44

This page last revised 4.1.2006.