|Contributed by Christoph Loddenkemper1, Stefan Hoecht3, Ioannis Anagnostopoulos1, Michael Hummel1, Bernhard Heine1, Gisela Stoltenburg-Didinger2, Harald Stein1|
|Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany,1Dept. of Pathology, Consultation and Reference Centre for Lymph Node Pathology and Haematopathology, 2Dept. of Neuropathology and 3Dept. of Radiation-Oncology|
|Published on line in June 2005|
The patient is a 62-year old man who was suffering from a chronic pyothorax after pneumectomy 44 years ago. In August 2002 a fenestration of the left thoracic wall was performed. Besides several serological signs of inflammation, NSE (neuron-specific enolase) was markedly elevated. Postoperatively, the patient complained of progressive ataxia and a cerebellar biopsy was performed. Despite treatment the patient died from aspergillus sepsis two month later and permission for autopsy was obtained.
X-ray examination of the chest showed an extensive shift of all mediastinal structures to the contralateral side due to a homogeneous mediastinal mass extending from the thoracic inlet to the diaphragm (Fig. 1).
The additional CT scan of thorax and abdomen confirmed the large confluent mediastinal tumor measuring 22 x 15 x 11 cm with displacement of trachea and heart and right-sided pleural effusion, which extended far beyond the limits of the diaphragm into the upper abdomen, where spleen and para-aortic lymph nodes were involved. After fenestration of the left hemithorax the extensive pleural calcifications were partially removed, the resulting defect covered with gaze and plasters (Fig. 2).
MRI of the head revealed a solitary neoplastic lesion of about 2 cm in diameter in the vermis cerebelli with marked enhancement after application of contrast material and consecutive slight enlargement of the ventricular system (Fig. 3).
On Giemsa stain the biopsy of the cerebellar lesion shows a diffuse proliferation of large cells with abundant basophilic cytoplasm and prominent central nucleoli (Fig. 4). By immunohistochemistry, only a small proportion of the tumor cells expressed the B-cell antigens CD79a (Fig. 5) and CD20. In addition, there was strong co-expression of the T-cell antigen CD2 (Fig. 6). Focally the tumor cells were positive for CD30 (Fig. 7) and the Epstein-Barr virus (EBV) encoded latent membrane protein (LMP)-1. Furthermore, immunohistochemistry and in situ hybridization showed strong nuclear expression of EBNA-2 (Fig. 8) and EBER transcripts (Fig. 9) in most tumor cells. No Kaposi sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8 (HHV8) could be detected.
Autopsy revealed a large mediastinal mass with extensive necrosis and a necrotic area with hemorrhage in the cerebellum. The B-cell nature of the lesion was confirmed by immunoglobulin heavy chain (IgH) gene PCR followed by GeneScan analysis demonstrating a clonal B-cell population with DNA amplificates of identical size (228 base pairs) in the mediastinal tumor (Fig. 10A) and the initial brain manifestation (Fig. 10B) without T-cell receptor (TCR) gene rearrangement.