Several reports of successful empirical treatment of idiopathic hypereosinophilic syndrome with imatinib led to the recent identification of the FIP1L1-PDGFRA fusion gene rearrangement, which characterizes a distinctive group of chronic eosinophilic leukemias. This fusion gene can be detected in eosinophils, neutrophils, mast cells, T cells, B cells and monocytes in FIP1L1-PDGFRA-positive hypereosinophilic patients suggesting a multilineage involvement. Furthermore, the same FIP1L1-PDGFRA rearrangement was identified in patients with hypereosinophilia and atypical mast cell proliferations, raising the question of a disease with two concomitant lines of differentiation. In addition, a recent report noted two cases with the association of FIP1L1-PDGFRA-positive chronic eosinophilic leukemia and T-cell lymphoblastic lymphoma (T-LBL). We report here the only third case of synchronous chronic eosinophilic leukemia and T-LBL, both associated with a FIP1L1-PDGFRA fusion transcript, confirming the occurrence of such disease and suggesting a clonal proliferation with two lines of differentiation probably arising from a primitive multipotent medullary stem cell.

It was recently demonstrated that classification of posttransplantation lymphoproliferative disorders (PT-LPDs) into morphological and molecular categories is clinically relevant. It was also reported that PT-LPD not associated with Epstein-Barr virus (EBV) had a more aggressive course than most lesions associated with EBV. Because the cyclin-dependent kinase inhibitor p16/INK4a has been reported to be frequently inactivated in high-grade lymphomas, we evaluated 17 PT-LPD to determine whether p16/ INK4a expression could be correlated to morphology, EBV detection, and a Ki-67 labeling index. We demonstrated that tumors with no p16/INK4a expression (n ‫؍‬ 8) had a predominantly monomorphic appearance, and most were EBV negative (respectively, 7/8 and 5/8), whereas lesions with p16/INK4a expression (n ‫؍‬ 9) were mostly polymorphic PT-LPD (6/9) (P ‫؍‬ 0.049) and associated with EBV (9/9) (P ‫؍‬ 0.015). In particular, strong p16/INK4a expression was observed in atypical immunoblasts and ReedSternberg-like cells. Furthermore, the proliferation index was significantly higher in tumors lacking p16/ INK4a expression than in other lesions (P ‫؍‬ 0.0008). Lymphoproliferative disorders (LPDs) are a major cause of morbidity in organ transplant recipients receiving immunosuppression, 1,2 varying between 1 and 12% of the graftees, for the most part according to the dose and duration of immunosuppressive therapy and the organ transplanted. 1,3-6 These tumors frequently involve extranodal sites and generally regress with reduction or withdrawal of immunosuppressive therapy, but some of them progress independently from the restoration of the immune system. It has been hypothesized that PT-LPDs arise from a polyclonal expansion of Epstein-Barr virus (EBV)-infected B cells and can evolve into a lymphoid tumor with the emergence of an oligoclonal or monoclonal dominant population. 7 PT-LPDs are usually classified into two subgroups, according to their appearance: polymorphic and monomorphic. 3 The latter closely resembles the diffuse large B-cell lymphoma (DLCL) of the Revised European American Lymphoma (REAL) classification. 8 Based on morphological and molecular analysis, Knowles et al 7 distinguished three main subgroups: 1) plasmacytic hyperplasia, 2) polymorphic B-cell hyperplasia and polymorphic B-cell lymphomas, and 3) malignant lymphoma or multiple myeloma, with the latter group being more frequently associated with genetic alterations, such as the inactivation of tumor suppressor gene p53 and the activation of c-myc and N-ras oncogenes. Moreover, Chadburn et al 9 recently showed the clinical relevance of this classification, as no response to aggressive clinical intervention was more frequently seen in patients with the lesions from the last group than those with the other tumors. Some patients with PT-LPDs that are not associated with EBV have a shorter survival time than those with EBV-positive lesions. 10 Expansion of B cells after organ transplantation should involve an excessive activation of the cell cycle, as in man...