Micronodular thymoma with lymphoid stroma / B-cell hyperplasia

Definition

Small tumour nodules are embedded within sheets of mature B cells with germinal centres. This was initially considered to be a variant of spindle cell thymoma¹ but the tumour nests may show a spectrum of appearances⁴, possibly corresponding to the spectrum of usual thymic neoplasms.

Epidemiology

This type accounts for only about 1% of all thymomas.

Clinical features

In a series of 18 cases, all were incidental findings in asymptomatic patients¹. There is no association with myasthenia gravis or other autoimmune disorders^1,3.

Macroscopic appearances

Most cases are encapsulated but some show infiltration of perithymic fat or pleural implants. These tumours commonly contain cystic areas.

Histopathology

The spindle cell variant is composed of small nodules of bland cells, lacking mitotic activity, as seen in conventional spindle cell thymoma. They do not form large lobules or fibrous septa but may locally coalesce. Only a few scattered lymphocytes are present within these nodules.

There may be numerous polygonal cells admixed with the spindle cells. They may form rosettes. The polygonal cells cells have large nuclei with nucleoli⁴. Alternatively, the polygonal cells may show atypia and focal keratinisation⁴. In some cases, the nests are irregular and the cells are cytologically atypical with features of lymphoepithelioma-like carcinoma⁴.

The lymphoid stroma contains prominent germinal centres. Plasma cells are prominent⁴. These follicles may show onion skin hyalinisation, resembling Castleman's disease³. These lymphoid areas are devoid of epithelial cells³.

In some studies, the cysts lack an epithelial lining¹. In others, they are described as being associated with glandular differentiation, the lining cells being picked out by EMA².

One case was in combination a type AB thymoma⁴, another with a type B2 thymoma². In one case, there was transition to lymphoepithelioma-like carcinoma.

Some cases may progress to low grade lymphoma (MALT lymphoma or follicular lymphoma)^0.

Immunohistochemistry

Epithelial cells :

	Cam5.2	positive in 60% of cases: positive in cysts0, strongly positive (based on 12 cases)1, 11/114
	AE1/AE3	11/114
	broad spectrum cytokeratin	weak focal positivity (based on 12 cases)1
	CK5/6	positive0
	CK7	positive in cysts0
	CK8	positive in cysts0
	CK19	positive0
	EMA	positive in cysts0, negative (based on 12 cases)1
	CD5	7/11 (positivity associated with malignancy of the epithelial cells)4
	CD20	negative in epithelial cells0, 0/53
	CD57	positive in 60% of cases0, 5/5 (strongly positive)3
	bcl-2	10/11 (weak in three cases)4
	chromogranin	0/94
	Synaptophysin	2/9 (focally positive in two cases)4

Lymphoid stroma. There is disagreement as to whether the lymphoid stroma is composed purely of B cells¹ or is a mix of B and T cells³.

	LCA	positive1
	CD20	positive1,3
	UCHL-1	a few positive cells1
	CD99	a few positive cells within the spindle cell nodules only1, 8/11 (positive in cases non-malignant epithelial cells)4
	CD1a	positive immature lymphocytes form a narrow band around the epithelial nodules0, a few positive cells within the spindle cell nodules only1, negative3
	CD3	negative1, a population of positive cells3
	CD5	negative1
	CD10	positive immature lymphocytes form a narrow band around the epithelial nodules0, germinal centre B-cells are positive0
	CD99	positive immature lymphocytes form a narrow band around the epithelial nodules0
	TdT	positive immature lymphocytes form a narrow band around the epithelial nodules0
	bcl-2	strong positivity of the mantles of the lymphoid follicles1
	kappa and lambda	polytypic1

Another study describes the lymphoid stroma as being composed of both B-cell areas with germinal centres and T-cell areas with large immature (CD1a+/CD99+) lymphocytes².

Differential diagnosis

• Type AB thymoma: the lymphocyte-rich areas of micronodular thymoma with lymphoid stroma do not contain epithelial cells.

• Reactive lymphoid hyperplasia of the thymus associated with myasthenia gravis.

• Lymphoid hyperplasia associated with acquired multilocular thymic cysts.

• Lymphoid hyperplasia in thymoma associated with myasthenia gravis

• Lymphoepithelioma-like carcinoma of the thymus: comedo necrosis, atypia and mitoses would be expected.

• Lymphoid hyperplasia associated with seminoma

• On biopsy, carcinoma or sarcoma metastatic to a lymph node. However, atypia and mitoses would be expected.

Management

Local resection is curative.

Prognosis

Limited follow up indicates a benign behavior.

References

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

¹Suster, S. and C. A. Moran (1999). "Micronodular thymoma with lymphoid B-cell hyperplasia: clinicopathologic and immunohistochemical study of eighteen cases of a distinctive morphologic variant of thymic epithelial neoplasm." Am J Surg Pathol 23(8): 955-62.

²Thomas De Montpreville, V., L. Zemoura, et al. (2002). "[Thymoma with epithelial micronodules and lymphoid hyperplasia: six cases of a rare and equivocal subtype]." Ann Pathol 22(3): 177-82.

³Pan, 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.

⁴Tateyama, H., Y. Saito, et al. (2001). "The spectrum of micronodular thymic epithelial tumours with lymphoid B-cell hyperplasia." Histopathology 38(6): 519-27.

Mende, S., M. Moschopulos, et al. (2004). "Ectopic micronodular thymoma with lymphoid stroma." Virchows Arch.

This page last revised 4.1.2006.

©SMUHT/PW Bishop