To date, no other case of a simultaneous involvement of the thymus by a thymic carcinoma and a B-CLL has been described in the English medical literature.
Only one case of a patient suffering from a B-cell chronic lymphocytic leukaemia/small lymphocytic lymphoma but associated with a thymoma has been reported by Khoury et al14
in 2003. They supposed that thymoma seem to be a predisposing factor for the development of secondary neoplasms.14
In general, metastases of intra- and extrathoracic tumours, lymphomas (Hodgkin and non-Hodgkin), thymic neoplasms and germ cell tumours are the most common malignancies occurring in the anterior mediastinum. Certain subtypes of thymomas and thymic carcinomas usually contain more or less lymphocytes, and so at first glance, lymphocytes are a normal feature of thymomas and certain subtypes of thymic carcinomas (eg, lymphoepithelial subtype).
However, in the case presented here, there were dense and circumscribed aggregates of lymphocytes even unusual for a thymic carcinoma of the lymphoepithelial subtype. These aggregates were also found in the adjunct fatty tissue of the mediastinum and in resected lymph nodes.
In some cases, for example, the so-called MNT, the detection of a lymphoma or leukaemic manifestation in the thymus is very difficult. In 1999, Suster and Moran15
published 18 cases of sometimes cystic thymomas, showing a micronodular growth pattern associated with lymphoid hyperplasia and named them MNT with B-cell hyperplasia.
They interpreted these cases as an unusual morphological variant of spindle cell thymomas with possible transition to lymphoepithelioma-like carcinomas because one histologic section showed areas of poorly differentiated squamous cell carcinoma.
Since that time, many reports of this special subtype have been documented. In 2004, Ströbel et al11
published a study with 18 patients suffering from MNT, demonstrating monoclonality of B-cell population in six cases by Ig heavy chain-directed PCR. In three of these six patients a MALT lymphoma could be detected. This example illustrates the difficulties of dealing with lymphomas within thymomas.
In addition to the rare occurrence of low grade B-cell lymphomas, other lymphomas have to be considered when dealing with malignant diseases of the thymus, especially Hodgkin lymphomas.11,16
In the mediastinum Hodgkin lymphomas are the most frequent malignant lymphomas (50–60%), sometimes with derivation from thymus tissue. Differential diagnosis between lymphocyte-rich thymomas, particularly type B1 thymomas and Hodgkin lymphomas (especially the lymphocyte predominant subtype), can be difficult.7,16
Besides, primary mediastinal (thymic) large B-cell lymphoma as well as precursor T-cell acute lymphoblastic leukaemia/lymphoblastic lymphoma may mimick an epithelial neoplasm of the thymus. Furthermore, the hyalinised blood vessels are sometimes very similar to Hassal's corpuscles, and the dense lymphocytic infiltrates, observed in Castleman's disease (angiofollicular lymph node hyperplasia) have to be distinguished from normal or hyperplastic thymic tissue.
Dependent on the subtype, thymic carcinomas often show a positive immunohistochemical staining for different epithelial markers such as AE 1+3, KL-1 or CK5/6 and sometimes for CD5 and c-kit.
CD5, a 67-kDa surface glycoprotein receptor, typically expressed on T lymphocytes, on the surface of peripheral blood cells and endothelial cells, is the only antigen which is also expressed by neoplastic cells in the B-cell lymphoproliferative disorders small lymphocytic lymphoma/chronic lymphocytic leukaemia and mantle cell lymphoma.17
These diseases are thought to arise from CD5-positive prefollicular centre lymphocytes. The reason for CD5 expression on malignant thymic cells is not fully understood.
In our present case CD5 was a helpful marker leading to the final diagnosis of a thymic carcinoma12,13
admixed by a lymphoid infiltrate of a chronic lymphocytic leukaemia.
In conclusion, our case report shows that lymphocytic infiltrates observed in many thymomas or thymic carcinomas may themselves be neoplastic. Lymphomas involve the thymus in relative high frequency, and therefore both the epithelial and the lymphocytic component of thymic tumours need to be thoroughly investigated and analysed.
- Tissue of the thymus regularly consist of lymphocytes, but we must always be aware, that a lymphocytic infiltration can also be a part of a leukaemia, lymphoma or metastasis of another carcinoma.
- In general, thymic carcinomas are aggressive malignancies with poor survival. Conventional chemotherapy for thymic carcinomas often results in minimal or no response.
- CD5, expressed by neoplastic cells in small lymphocytic lymphoma/chronic lymphocytic leukaemia, mantle cell lymphoma and most of thymic carcomas led to the confirmed diagnosis of a thymic carcinoma associated with a B-CLL.