Ewing tumor after treatment of Ki-1+ anaplastic large cell lymphoma. Therapy-associated secondary neoplasm or unrelated coincidence?

We report on a 20-year-old woman who developed a pelvic small round cell tumor with lung metastases 8 years after diagnosis and successful treatment for Ki-1-positive anaplastic large cell lymphoma (Ki-1+ ALCL) with histiocytic differentiation. Molecular genetic detection of EWS/FLI-1 fusion gene expression in the second tumor by RT-PCR unambiguously confirmed the histopathologic diagnosis of Ewing tumor (ET), whereas no evidence for the presence of this specific gene rearrangement was obtained in a retrospective analysis of the lymphoma tissue. In contrast, expression of a NPM/ALK chimeric gene was observed which was absent in the ET. Moreover, the lymphoma contained a monoallelic D delta 2-D delta 3 T-cell receptor gene rearrangement which was also absent in the ET. Thus, our histopathologic, immunohistochemical, and, in particular, molecular genetic studies support the notion that these tumors were most probably pathogenetically unrelated. Since this is the first report describing such an association between a non-Hodgkin's lymphoma and ET and, since the latter has only rarely been observed as a second malignant neoplasm, it remains a matter of speculation whether in this patient ET developed as a therapy-related secondary neoplasm or independently from the lymphoma as a consequence of either genetic tumor predisposition or mere accidental coincidence.