FINAL DIAGNOSIS: BRAIN MANIFESTATION OF A PYOTHORAX-ASSOCIATED LYMPHOMA (PAL).
Pyothorax-associated lymphoma (PAL) is a rare non-Hodgkin's lymphoma (NHL) developing in the pleural cavity after a 20- to 64-year history of chronic pyothorax resulting from artificial pneumothorax for the treatment of pulmonary tuberculosis. Following the first report in 1987, the majority of PALs have been described in Japan. Histomorphologically, PALs can be regarded as a variant of diffuse large B-cell lymphoma (DLBCL), often displaying immunoblastic or plasmablastic features. There is a strong association of PAL with Epstein-Barr virus (EBV)infection[4;5]. In the tumor cells EBV-enconded nuclear RNAs can be demonstrated by EBER in situ hybridization. Immunohistochemistry reveals expression of the EBV-encoded latent membrane protein (LMP)-1 and EBV-encoded nuclear antigen (EBNA)-2, consistent with type III virus latency which is also found in immunosuppression-associated lymphoproliferations like post-transplant lymphoproliferative disorders (PTLDs). It has been suggested that the chronic inflammation of the pleura and the production of immunosuppressive cytokines (e.g. IL6 and IL10) may favour the clonal proliferation of EBV-transformed B-cells[6,7].
Among the largest series of 106 PALs collected through a nationwide survey in Japan, there was only one case with a brain manifestation in addition to tumor masses in the pleura, although central nervous system (CNS) involvement was detected in 5 out of 36 (14%) patients when an autopsy had been performed. In our case, autopsy revealed a large pleural mass with invasion of the adjacent mediastinum and extensive necrosis. Numerous previous pleural biopsies had not been diagnostic because only necrotic tissue was obtained. The morphology and the immunophenotype of the tumor cells in the brain biopsy, in conjunction with the history of long-standing pyothorax allowed to make the diagnosis of PAL. Besides the typical EBV-protein expression pattern, the tumor cells had a CD10-/BCL-6-/IRF4+/CD138+ phenotype in support of an origin from late germinal center (GC)/post GC B cells, which is in harmony with the findings of Petitjean and co-authors. In addition, the tumor cells showed an aberrant dual B- and T-cell phenotype with expression of CD2, a phenomenon which has been reported in a proportion of PALs[8;9]. Interestingly, aberrant expression of T-cell antigens in B-cell lymphoma can also be found in other EBV associated lymphomas like primary effusion lymphoma (PEL) and post-transplant associated lymphoproliferative disease (PTLD). In contrast to PAL, PEL is related to human immune deficiency virus (HIV) infection and is associated with KSHV/HHV8. Although EBV associated primary CNS lymphoma most often is HIV-related or occurs in the setting of a PTLD, in cases with plasmablastic features clinical correlation is advisable to exclude PAL.
To best of our knowledge, this is the first case of a pyothorax associated lymphoma (PAL) initially diagnosed on brain biopsy.
Contributed by Contributed by Christoph Loddenkemper, Stefan Hoecht, Ioannis Anagnostopoulos, Bernhard Heine, Gisela Stoltenburg-Didinger, Harald Stein