Type B3 thymoma

Definition

An organotypic thymoma composed of round or polygonal epithelial cells with limited atypia, admixed with relatively few lymphocytes.

Synonyms

Epithelial thymoma, atypical thymoma, well-differentiated thymic carcinoma2, squamoid thymoma.

Epidemiology

Type B3 accounts for 7-25% of thymomas.

Clinical features

Myasthenia gravis is common. Red cell aplasia, hypogammaglobulinaemia, other autoimmune conditions and SVC obstruction are rare presentations. Regression may result in cyst formation or calcification.

Radiology

Macroscopic appearances

These are invasive tumours and are usually not encapsulated. The tumour is divided by white fibrous septa. Masaoka stage varies: stage I; 0% stage II; 16%, stage III; 59%, stage IV; 25%2.

Histopathology

The epithelial cells are round or polygonal, smaller than those of type B2 thymoma with less prominent nucleoli, and form sheets. They vary from small with inconspicuous nucleoli to large with nuclei and nucleoli, similar to those of type B2 thymoma. The epithelial cells may form squamoid foci but intercellular bridges are not apparent. Focal keratinisation may mimic Hassall's corpuscles. Perivascular spaces, with palisading of epithelial cells, occur. Lymphocytes are relatively sparse. The presence of lymphoid follicles is associated with myasthenia gravis.

Steroid treatment may produce regression with the accumulation of foam cells.

Variants:

• with focally greater nuclear atypia. If anaplasia is marked but organotypic features are retained, the tumour should be designated as "B3 thymoma with anaplasia".

• large cell variant with epithelial cells resembling those of type B2 thymoma.

• clear cell variant with focal loss of lymphocytes.

• spindle cell variant

• combined B2 / B3 thymoma is common

• combined B3 thymoma / thymic carcinoma is rare

Immunohistochemistry

Ultrastructure

Cytogenetics

There are gains of chromosome 1q and losses of chromosomes 6 and 13q1. Almost all cases are aneuploid.

Differential diagnosis

• Type A thymoma also has few lymphocytes, but the epithelial cells are spindle or oval. In contrast to the spindle cell variant of type B3 thymoma, atypia is lacking, there is reticulin around individual cells and there is a lack of perivascular spaces with epithelial palisades.

• Type B2 thymoma has abundant lymphocytes. Epithelial cells do not form confluent sheets. It lacks the focal positivity for EMA characteristic of type B3.

• Low grade squamous carcinoma shows more marked epidermoid features, including intercellular bridges and lacks immature lymphocytes.

Management

The tumour is often not resectable at presentation.

Prognosis

Local recurrence occurs in about 15% of cases and metastases in up to 20% of cases. The prognosis is the worst among the organotypic thymomas, with survival of 80% at 5 years and 40-70% at 10 years0,2. Metastases are commonly to lung, liver, bone and soft tissues.

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

5 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.

©SMUHT/PW Bishop